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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Leber Congenital Amaurosis – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_author" content="Richard G Weleber">
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<meta name="citation_keywords" content="Spermatogenesis-associated protein 7">
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<meta name="citation_keywords" content="Tubby-related protein 1">
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<meta name="citation_keywords" content="X-linked retinitis pigmentosa GTPase regulator-interacting protein 1">
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class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><p class="vip-notice retraction"><strong>This publication is provided for historical reference only and the information may be out of date.</strong></p><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK1298_"><span class="title" itemprop="name">Leber Congenital Amaurosis – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY</span></h1><div itemprop="alternativeHeadline" class="subtitle whole_rhythm">Synonym: LCA</div><p class="contribs">Weleber RG, Francis PJ, Trzupek KM, et al.</p><p class="fm-aai"><a href="#_NBK1298_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 42 minutes</em></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="lca.Summary" itemprop="description"><h2 id="_lca_Summary_">Summary</h2><p><b>NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE. SEE</b>
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<a href="/books/n/gene/lca-ov/?report=reader"><b>LEBER CONGENITAL AMAUROSIS / EARLY-ONSET SEVERE RETINAL DYSTROPHY OVERVIEW</b></a><b>.</b></p><div><h4 class="inline">Clinical characteristics.</h4><p>Leber congenital amaurosis (LCA), a severe dystrophy of the retina, typically becomes evident in the first year of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus. Visual acuity is rarely better than 20/400. A characteristic finding is Franceschetti's oculo-digital sign, comprising eye poking, pressing, and rubbing. The appearance of the fundus is extremely variable. While the retina may initially appear normal, a pigmentary retinopathy reminiscent of retinitis pigmentosa is frequently observed later in childhood. The electroretinogram (ERG) is characteristically "nondetectable" or severely subnormal.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of LCA is established by clinical findings. Pathogenic variants in 17 genes are known to cause LCA: <i>GUCY2D</i> (locus name: LCA1), <i>RPE65</i> (LCA2), <i>SPATA7</i> (LCA3), <i>AIPL1</i> (LCA4), <i>LCA5</i> (LCA5), <i>RPGRIP1</i> (LCA6), <i>CRX</i> (LCA7), <i>CRB1</i> (LCA8), <i>NMNAT1</i> (LCA9), <i>CEP290</i> (LCA10), <i>IMPDH1</i> (LCA11), <i>RD3</i> (LCA12), <i>RDH12</i> (LCA13), <i>LRAT</i> (LCA14)<i>, TULP1</i> (LCA15)<i>,</i>
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<i>KCNJ13</i> (LCA16), and <i>IQCB1</i>. Together, pathogenic variants in these genes are estimated to account for more than half of all LCA diagnoses. At least one other disease locus for LCA has been reported, but the gene is not known.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Treatment is supportive. Children and their parents should be referred to programs for the visually impaired child within their state or locality. Affected individuals benefit from correction of refractive error, use of low-vision aids when possible, and optimal access to educational and work-related opportunities.</p><p><i>Prevention of secondary complications:</i> When possible children should be discouraged from repeatedly poking and pressing on their eyes.</p><p><i>Surveillance:</i> Periodic ophthalmic evaluation for assessment of vision, trials of correction for refractive error, and, in those with residual vision, assessment of the presence of amblyopia, glaucoma, or cataract.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>Most often LCA is inherited in an autosomal recessive manner. At conception, each sib of an individual with recessively inherited LCA has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members is possible if the pathogenic variants in the family are known. Prenatal testing for pregnancies at increased risk is possible through laboratories offering either testing for the gene of interest or custom testing. Rarely, LCA is inherited in an autosomal dominant manner as a result of a pathogenic variant in <i>CRX</i>; the possibility of autosomal dominant inheritance resulting from a <i>de novo</i>
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<i>CRX</i> pathogenic variant should be considered in individuals with LCA and no family history of the disease.</p></div></div><div id="lca.Diagnosis"><h2 id="_lca_Diagnosis_">Diagnosis</h2><div id="lca.Clinical_Diagnosis"><h3>Clinical Diagnosis</h3><p>The form of congenital or early-infantile blindness known as Leber congenital amaurosis (LCA) was first defined by Theodor Leber in 1869 and 1871 on the basis of clinical findings [<a class="bibr" href="#lca.REF.leber.1869.1" rid="lca.REF.leber.1869.1">Leber 1869</a>, <a class="bibr" href="#lca.REF.leber.1871.249" rid="lca.REF.leber.1871.249">Leber 1871</a>]. While no universally agreed-upon diagnostic criteria are available, the following features are highly suggestive:</p><ul><li class="half_rhythm"><div><b>Blindness or severe visual impairment</b> presenting in infancy, frequently before age six months. Individuals with LCA usually do not achieve visual acuity better than 20/400 [<a class="bibr" href="#lca.REF.cremers.2002.1169" rid="lca.REF.cremers.2002.1169">Cremers et al 2002</a>].</div></li><li class="half_rhythm"><div><b>Extinguished or severely reduced scotopic and photopic electroretinogram (ERG).</b> Normal ERG responses rule out a diagnosis of LCA. Visual evoked responses are variable.</div></li><li class="half_rhythm"><div><b>The oculo-digital sign,</b> characterized by poking, rubbing, and/or pressing of the eyes [<a class="bibr" href="#lca.REF.fazzi.2003.13" rid="lca.REF.fazzi.2003.13">Fazzi et al 2003</a>]. The oculo-digital sign has been claimed to be virtually pathognomonic for LCA; however, it can also be seen in other syndromic forms of severe vision impairment.</div></li><li class="half_rhythm"><div><b>Family history</b> typically consistent with autosomal recessive inheritance</div></li></ul><p>Individuals with LCA also frequently exhibit the following:</p><ul><li class="half_rhythm"><div>Sluggish or near-absent pupillary reactions reflecting the severe retinal dysfunction</div></li><li class="half_rhythm"><div>Nystagmus that is pendular or roving and present in all positions of gaze</div></li><li class="half_rhythm"><div>High hyperopia (>5 diopters), which is thought to result from impaired emmetropization (the ability of the eye to accommodate to visual stimuli) as a consequence of early-onset visual impairment</div></li><li class="half_rhythm"><div>Photophobia</div></li><li class="half_rhythm"><div>Keratoconus, a noninflammatory, self-limiting axial ectasia of the central cornea. Keratoconus can significantly interfere with vision in normal individuals but usually does not become a vision-limiting factor in LCA.</div></li></ul><p><b>Retinal findings.</b> No retinal lesion is diagnostic of LCA or specific for certain genetic subtypes. Although fundus abnormalities are frequently present later in life, infants with LCA typically show either a normal fundus appearance or only subtle retinal pigment epithelial (RPE) granularity, retinal vessel attenuation and, uncommonly, various stages of macular atrophy.</p><p>Of note, three more specific retinal phenotypes can be observed:</p><ul><li class="half_rhythm"><div>Preserved para-arteriolar retinal pigment epithelium (PPRPE) in individuals with <i>CRB1</i> pathogenic variants</div></li><li class="half_rhythm"><div>"Translucent RPE," white dots, and a peculiar star-shaped maculopathy in individuals with <i>RPE65</i> pathogenic variants</div></li><li class="half_rhythm"><div>A progressive macular atrophic lesion presenting in infancy or later in some individuals. Because of its sharply defined borders, this lesion has been at times called a “macular coloboma.” While it has been reported to occur with pathogenic variants in <i>AIPL1</i> and <i>CRB1</i>, the correlation of this LCA phenotype is most prominent with pathogenic variants in <i>NMNAT1</i> [<a class="bibr" href="#lca.REF.chiang.2012.972" rid="lca.REF.chiang.2012.972">Chiang et al 2012</a>, <a class="bibr" href="#lca.REF.falk.2012.1040" rid="lca.REF.falk.2012.1040">Falk et al 2012</a>, <a class="bibr" href="#lca.REF.koenekoop.2012.1035" rid="lca.REF.koenekoop.2012.1035">Koenekoop et al 2012</a>, <a class="bibr" href="#lca.REF.perrault.2012.975" rid="lca.REF.perrault.2012.975">Perrault et al 2012</a>].</div></li></ul></div><div id="lca.Molecular_Genetic_Testing"><h3>Molecular Genetic Testing</h3><p><b>Genes.</b> Pathogenic variants in seventeen genes are known to cause Leber congenital amaurosis (LCA) (<a href="/books/NBK1298/table/lca.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figoblcaTmoleculargenetictestingusedin">Table 1</a>).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTmoleculargenetictestingusedin"><a href="/books/NBK1298/table/lca.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figoblcaTmoleculargenetictestingusedin"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.molecular_genetic_testing_used_in"><a href="/books/NBK1298/table/lca.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figoblcaTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Leber Congenital Amaurosis </p></div></div></div><div id="lca.Testing_Strategy"><h3>Testing Strategy</h3><p><b>To establish the diagnosis in a proband.</b>
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<a class="bibr" href="#lca.REF.hanein.2004.306" rid="lca.REF.hanein.2004.306">Hanein et al [2004]</a> proposed a clinical flowchart using the presence or absence of photophobia, night blindness, hyperopia, macular/peripheral retinal abnormalities, and measurable acuity to help direct the order of genes selected for molecular studies.</p><ul><li class="half_rhythm"><div><b>Multigene testing.</b> Consider using a multigene Leber congenital amaurosis panel that includes many genes associated with LCA<i>.</i> These panels vary by methods used and genes included; thus, the ability of a panel to detect a causative variant or variants in any given individual also varies. For an introduction to multigene panels click <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels">here</a>. More detailed information for clinicians ordering genetic tests can be found <a href="/books/n/gene/app5/?report=reader#app5.Multigene_Panels_FAQs">here</a>.</div></li></ul><p><b>Carrier testing for autosomal recessive LCA for relatives</b>
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<b>at-risk</b> requires prior identification of the pathogenic variants in the family. Note: Carriers are heterozygotes for these autosomal recessive disorders and are not at risk of developing the disorder.</p><p><b>Prenatal diagnosis and preimplantation genetic testing</b> for at-risk pregnancies require prior identification of the pathogenic variant(s) in the family.</p></div></div><div id="lca.Clinical_Characteristics"><h2 id="_lca_Clinical_Characteristics_">Clinical Characteristics</h2><div id="lca.Clinical_Description"><h3>Clinical Description</h3><p>Leber congenital amaurosis (LCA) has retinal, ocular, and extraocular features and occasionally, systemic associations [<a class="bibr" href="#lca.REF.fazzi.2003.13" rid="lca.REF.fazzi.2003.13">Fazzi et al 2003</a>].</p><p><b>Retina.</b> The retina may appear normal initially; later, a variety of abnormalities may develop either in isolation or combination:</p><ul><li class="half_rhythm"><div>"Macular coloboma"; not a true coloboma, but reflecting discrete chorioretinal degeneration and atrophy centered about the fovea</div></li><li class="half_rhythm"><div>"Bone-spicule" intraretinal pigment migration</div></li><li class="half_rhythm"><div>Widespread subretinal flecks resembling retinitis punctata albescens</div></li><li class="half_rhythm"><div>"Marbled" fundus</div></li><li class="half_rhythm"><div>Discrete pigmented nummular lesions at the level of the retinal pigment epithelium (RPE)</div></li><li class="half_rhythm"><div>Optic disc abnormalities: swelling, drusen formation, and peripapillary neovascularization</div></li></ul><p><b>Oculo-digital sign.</b> The characteristic extraocular sign in LCA is Franceschetti's oculo-digital sign, comprising three components: eye poking, pressing, and rubbing. It is not known why this behavior occurs. The major sequelum is enophthalmos, a physical defect in which the eye recedes into the orbit, presumably from atrophy of orbital fat. Keratoconus has been said to result from the repetitive trauma to the cornea, but others have suggested that this may be a feature of LCA itself.</p><p><b>Intellectual disability.</b> Rarely, LCA is seen in association with neurodevelopmental delay, intellectual disability, and oculomotor apraxia-type behavior. However, many if not most of the historical reports date to earlier studies in which systemic phenocopies of LCA (see <a href="#lca.Differential_Diagnosis">Differential Diagnosis</a>) were not considered or ruled out. Still, some studies suggest that as many as 20% of children with LCA without associated anomalies develop intellectual disability [<a class="bibr" href="#lca.REF.schuil.1998.294" rid="lca.REF.schuil.1998.294">Schuil et al 1998</a>]. Whether these individuals represent undiagnosed systemic disorders or a genetic subtype of LCA is unknown.</p><p>Prior to the identification of <i>CEP290</i>, none of the molecularly defined types of LCA was shown to be associated with intellectual disability or neurodevelopmental degeneration. <a class="bibr" href="#lca.REF.perrault.2007.416" rid="lca.REF.perrault.2007.416">Perrault et al [2007]</a> reported a subset of individuals (15%) with <i>CEP290</i>-related LCA who have intellectual disability or autistic features, but no other extraretinal manifestations. Two of the six individuals in the study with intellectual disability or autism were later reclassified as having <a href="/books/n/gene/joubert/?report=reader">Joubert syndrome</a> based on the presence of the “molar tooth” sign on MRI. In others, the MRI was apparently normal.</p><p><b>Visual impairment.</b> Profound visual impairment is usually present from birth. One third of individuals with LCA have no perception of light. The visual impairment is generally stable or very slowly progressive. Occasionally in the early stages, a mild degree of visual improvement is observed. This improvement has been attributed to development of the central visual pathways rather than retinal maturation. Sustained improvements in acuity, visual field, and electrophysiologic measurements have been reported in one individual with a <a href="/books/NBK1298/table/lca.T.crx_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrxpathogenicvariantsdiscussed">c.529delG</a> pathogenic variant in <i>CRX</i> [<a class="bibr" href="#lca.REF.koenekoop.2002b.49" rid="lca.REF.koenekoop.2002b.49">Koenekoop et al 2002b</a>]. Loss of visual acuity typically results from keratoconus, cataract, or evolving macular lesions.</p><p><b>Carriers.</b> Carriers (heterozygotes) are usually asymptomatic; however, some heterozygotes for <i>GUCY2D</i> pathogenic variants have been shown to have mild cone dysfunction measured by decreased cone responses on electroretinogram [<a class="bibr" href="#lca.REF.koenekoop.2002a.1325" rid="lca.REF.koenekoop.2002a.1325">Koenekoop et al 2002a</a>]. However, this is not associated with any findings on ophthalmologic examination and does not appear to interfere with vision.</p></div><div id="lca.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>A number of genotype-phenotype correlations appear to have emerged.</p><p><b><i>GUCY2D</i> (LCA1).</b> Pathogenic variants in <i>GUCY2D</i>, which encodes retinal guanylyl cyclase 1 (RetGC), have been associated with a congenital severe cone-rod dystrophy characterized by photophobia, high hyperopia, and poor but stable vision with no visual improvement [<a class="bibr" href="#lca.REF.perrault.1999.1225" rid="lca.REF.perrault.1999.1225">Perrault et al 1999</a>, <a class="bibr" href="#lca.REF.lorenz.2000.2735" rid="lca.REF.lorenz.2000.2735">Lorenz et al 2000</a>, <a class="bibr" href="#lca.REF.hanein.2004.306" rid="lca.REF.hanein.2004.306">Hanein et al 2004</a>]. However, <a class="bibr" href="#lca.REF.perrault.2005.222" rid="lca.REF.perrault.2005.222">Perrault et al [2005]</a> described a man with early-onset RP resulting from the homozygous 4-bp pathogenic variant <a href="/books/NBK1298/table/lca.T.gucy2d_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTgucy2dpathogenicvariantsdiscuss">p.[His1079GlnfsTer54]</a>+[His1079GlnfsTer54] in <i>GUCY2D</i>. The man has night blindness, peripheral vision loss, and preservation of central vision typical of RP. Unlike most null variants described in <i>GUCY2D</i> to date, p.His1079GlnfsTer54 is predicted to result in an elongation of the protein and residual protein function [<a class="bibr" href="#lca.REF.perrault.2005.222" rid="lca.REF.perrault.2005.222">Perrault et al 2005</a>].</p><p><b><i>RPE65</i> (LCA2)<i>.</i></b> Pathogenic variants in <i>RPE65</i> have been associated with night blindness, some transient improvement in vision, and eventual progressive visual loss [<a class="bibr" href="#lca.REF.perrault.1999.1225" rid="lca.REF.perrault.1999.1225">Perrault et al 1999</a>, <a class="bibr" href="#lca.REF.dharmaraj.2000b.135" rid="lca.REF.dharmaraj.2000b.135">Dharmaraj et al 2000b</a>]. Lorenz found that four individuals with LCA and <i>RPE65</i> pathogenic variants had measurable visual acuity at age six to ten years, despite severe visual impairment from infancy and nystagmus in three of the four [<a class="bibr" href="#lca.REF.lorenz.2000.2735" rid="lca.REF.lorenz.2000.2735">Lorenz et al 2000</a>]. Photophobia was not a feature and all individuals had preservation of measurable peripheral vision. Rod ERG responses were undetectable, whereas cone ERG responses were detectable in early childhood.</p><p><a class="bibr" href="#lca.REF.paunescu.2005.417" rid="lca.REF.paunescu.2005.417">Paunescu et al [2005]</a> presented detailed follow-up data on three adult sibs with LCA suggesting that photophobia and progressive visual loss occur with age. Using a genotyping microarray, <a class="bibr" href="#lca.REF.zernant.2005.3052" rid="lca.REF.zernant.2005.3052">Zernant et al [2005]</a> found that only five of 69 individuals with LCA (7%) with detectable pathogenic variants had an <i>RPE65</i> genotype. This detection rate, lower than previous studies would predict, suggests that allelic variation in <i>RPE65</i> may be more highly associated with early-onset severe retinal dystrophy than with classic LCA [Authors, personal observation].</p><p>Individuals with pathogenic variants in <i>RPE65</i> may also demonstrate "translucent RPE," white dots, and a peculiar star-shaped maculopathy [<a class="bibr" href="#lca.REF.weleber.2011.292" rid="lca.REF.weleber.2011.292">Weleber et al 2011</a>].</p><p><b><i>AIPL1</i> (LCA4)<i>.</i></b>
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<a class="bibr" href="#lca.REF.dharmaraj.2004.1029" rid="lca.REF.dharmaraj.2004.1029">Dharmaraj et al [2004]</a> studied 303 individuals with LCA and found that 26 probands (8.5% of their cohort) harbored homozygous or heterozygous pathogenic variants in <i>AIPL1</i>. Fourteen (54%) of these 26 individuals had at least one allele with the <a href="/books/NBK1298/table/lca.T.aipl1_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figoblcaTaipl1pathogenicvariantsdiscusse">p.Trp278Ter</a> pathogenic variant. The authors described the phenotype of LCA in these individuals and compared them to those observed and reported with LCA from pathogenic variants in <i>GUCY2D, RPE65, CRX, CRB1,</i> and <i>RPGRIP1</i>. The phenotype of LCA in individuals with <i>AIPL1</i> pathogenic variants was found to be relatively severe, with maculopathy and marked bone-spicule pigmentary retinopathy in most and keratoconus and cataract in a large subset. The authors conclude that the visual loss associated with mutation of <i>AIPL1</i> is similar in severity to that observed with mutation of <i>GUCY2D</i>. <a class="bibr" href="#lca.REF.pennesi.2011.8166" rid="lca.REF.pennesi.2011.8166">Pennesi et al [2011]</a> reported a unique electroretinogram phenotype characterized by slow insensitive scotopic responses (SISR), which if present on testing may suggest this genetic form of LCA.</p><p><b><i>LCA5</i> (LCA5).</b> In the Old River Brethren family originally linked to LCA5, severe visual dysfunction, nystagmus, the oculodigital sign, and a normal fundus were noted in all affected individuals in infancy. High hyperopia and attenuated retinal vasculature developed over time, and ERG recordings were severely reduced [<a class="bibr" href="#lca.REF.dharmaraj.2000a.319" rid="lca.REF.dharmaraj.2000a.319">Dharmaraj et al 2000a</a>]. <a class="bibr" href="#lca.REF.den_hollander.2007.889" rid="lca.REF.den_hollander.2007.889">Den Hollander et al [2007]</a> defined pathogenic variants within <i>LCA5</i> in multiple unrelated families, all of whom presented with a similar, severe congenital retinal dystrophy. One of the families, reported earlier by <a class="bibr" href="#lca.REF.mohamed.2003.473" rid="lca.REF.mohamed.2003.473">Mohamed et al [2003]</a>, developed macular abnormalities including macular coloboma and atrophy. Renal, neurologic, cognitive, and hepatic functions have been normal across all affected families. Individuals with LCA5 have been shown to have spared photoreceptors, mostly in the macular region, that are adjacent to disorganized retina [<a class="bibr" href="#lca.REF.jacobson.2009.1098" rid="lca.REF.jacobson.2009.1098">Jacobson et al 2009</a>].</p><p><b><i>RPGRIP1</i> (LCA6).</b>
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<a class="bibr" href="#lca.REF.hanein.2004.306" rid="lca.REF.hanein.2004.306">Hanein et al [2004]</a> described the following features as characteristic of <i>RPGRIP1</i> pathogenic variants: early photophobia, hypermetropia less than +7 diopters, and visual acuity in the range of 20/400 to count fingers (CF). In follow up of individuals with LCA, <a class="bibr" href="#lca.REF.galvin.2005.919" rid="lca.REF.galvin.2005.919">Galvin et al [2005]</a> found that visual acuity in children with pathogenic variants in <i>RPGRIP</i> frequently progresses to light perception (LP) or no light perception (NLP) within the first decade of life.</p><p><b><i>CRX</i> (LCA7).</b> Pathogenic variants in <i>CRX</i> have also been reported to be associated with stable vision [<a class="bibr" href="#lca.REF.dharmaraj.2000b.135" rid="lca.REF.dharmaraj.2000b.135">Dharmaraj et al 2000b</a>] or even some modest improvement [<a class="bibr" href="#lca.REF.koenekoop.2002b.49" rid="lca.REF.koenekoop.2002b.49">Koenekoop et al 2002b</a>]. Single or double base-pair deletions of the gene account for only the dominant forms of LCA, as a result of either an inherited dominant pathogenic variant or a <i>de novo</i> mutational event [<a class="bibr" href="#lca.REF.sohocki.1998.1307" rid="lca.REF.sohocki.1998.1307">Sohocki et al 1998</a>, <a class="bibr" href="#lca.REF.rivolta.2001.488" rid="lca.REF.rivolta.2001.488">Rivolta et al 2001</a>, <a class="bibr" href="#lca.REF.tzekov.2001.1319" rid="lca.REF.tzekov.2001.1319">Tzekov et al 2001</a>, <a class="bibr" href="#lca.REF.perrault.2003.e90" rid="lca.REF.perrault.2003.e90">Perrault et al 2003</a>].</p><p><b><i>CRB1</i> (LCA8).</b> Night blindness is a constant feature of LCA resulting from <i>CRB1</i> pathogenic variants. <a class="bibr" href="#lca.REF.jacobson.2003.1073" rid="lca.REF.jacobson.2003.1073">Jacobson et al [2003]</a> found thick unlaminated retinas by optical coherence tomography (OCT) in individuals with LCA and <i>CRB1</i> defects. Although some individuals with RP resulting from <i>CRB1</i> pathogenic variants have the fundus appearance of preserved para-arteriolar RPE (PPRPE), no individuals with LCA resulting from <i>CRB1</i> pathogenic variants have yet been reported to have PPRPE [<a class="bibr" href="#lca.REF.den_hollander.2001.198" rid="lca.REF.den_hollander.2001.198">den Hollander et al 2001</a>].</p><p><b><i>CEP290</i> (LCA10).</b> Two independent series of individuals with <i>CEP290</i> pathogenic variants [<a class="bibr" href="#lca.REF.den_hollander.2006.556" rid="lca.REF.den_hollander.2006.556">den Hollander et al 2006</a>, <a class="bibr" href="#lca.REF.perrault.2007.416" rid="lca.REF.perrault.2007.416">Perrault et al 2007</a>] confirm a “typical” ophthalmologic LCA phenotype consisting of a severe infantile-onset cone-rod dystrophy with high hyperopia and severe ERG abnormalities. In addition, each series described a single individual with a reticular pigment epithelium in the peripheral retina with multiple white dots. This specific phenotype has not been reported with the other LCA-associated genes.</p><p>Extraretinal findings were described in a subset of individuals in Perrault’s study, and primarily included hypotonia and ataxia or intellectual disability and autistic behaviors. In fact, six of 40 families segregating <i>CEP290</i> pathogenic variants were reported to have at least one affected individual with intellectual disability or autism. Two of those individuals were later reclassified as having <a href="/books/n/gene/joubert/?report=reader">Joubert syndrome</a> on the basis of the classic "molar tooth" sign on MRI. Interestingly, a high degree of intrafamilial variability was observed with respect to the presence or absence of intellectual disability, leading the authors to suggest the possibility of a third allele or modifier gene in the development of cognitive disability in this subtype of LCA.</p><p><b><i>IMPDH1</i> (LCA11).</b>
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<a class="bibr" href="#lca.REF.bowne.2006.34" rid="lca.REF.bowne.2006.34">Bowne et al [2006]</a> described heterozygous, apparently <i>de novo</i>
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<i>IMPDH1</i> pathogenic variants in two unrelated individuals with a diagnosis of LCA. <i>IMPDH1</i> is a gene previously known to be associated with autosomal dominant <a href="/books/n/gene/rp-overview/?report=reader">retinitis pigmentosa</a>. The clinical description of one of the individuals reported by <a class="bibr" href="#lca.REF.bowne.2006.34" rid="lca.REF.bowne.2006.34">Bowne et al [2006]</a> fits the classic LCA phenotype; the other appears to have an early-onset retinal dystrophy better fitting the diagnosis of SECORD (see <a href="#lca.Differential_Diagnosis">Differential Diagnosis</a>). Additional studies must be undertaken to assess the prevalence of <i>IMPDH1</i> pathogenic variants in the LCA population.</p><p><b><i>RDH12</i> (LCA13).</b> In a further study of the individuals studied by <a class="bibr" href="#lca.REF.hanein.2004.306" rid="lca.REF.hanein.2004.306">Hanein et al [2004]</a>, <a class="bibr" href="#lca.REF.perrault.2004.639" rid="lca.REF.perrault.2004.639">Perrault et al [2004]</a> identified 11 distinct pathogenic variants of <i>RDH12</i> in 8/44 individuals with LCA characterized by congenital severe progressive rod-cone dystrophy. All eight with <i>RDH12</i> pathogenic variants had a clinical course similar to that of individuals with <i>RPE65</i> pathogenic variants: mild or absent hyperopia, transient improvement of visual acuity, and eventual macular atrophy with severe disease progression. Loss of visual acuity, however, occurred at an earlier age in those with <i>RDH12</i> pathogenic variants than in those with <i>RPE65</i> pathogenic variants. No <i>RDH12</i> pathogenic variants were observed in persons with LCA presenting with the congenital stationary cone-rod dystrophy form of the disease.</p><p><i>IQCB1</i>. Individuals with pathogenic variants in <i>IQCB1</i> often have greater loss of rod function than loss of cone function. All newly diagnosed individuals with LCA should have testing for pathogenic variants in this gene and, if found, should undergo careful monitoring of renal function.</p><p><b>Keratoconus</b> has been reported to occur in individuals with specific pathogenic variants in the <i>CRB1</i> and <i>AIPL1</i> genes [<a class="bibr" href="#lca.REF.hameed.2000.629" rid="lca.REF.hameed.2000.629">Hameed et al 2000</a>].</p><p><b>Photophobia and night blindness.</b>
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<a class="bibr" href="#lca.REF.hanein.2004.306" rid="lca.REF.hanein.2004.306">Hanein et al [2004]</a> performed molecular screening on 179 unrelated individuals with LCA and reported the genotype-phenotype correlations on 85 who were found to harbor pathogenic variants on one or both alleles in one of seven LCA-associated genes. Frequencies of mutation in each gene were as follows:</p><ul><li class="half_rhythm"><div><b><i>GUCY2D</i>.</b> 21.2% (38/179 families)</div></li><li class="half_rhythm"><div><b><i>CRB1</i>.</b> 10% (18/179)</div></li><li class="half_rhythm"><div><b><i>RPE65</i>.</b> 6.1% (11/179)</div></li><li class="half_rhythm"><div><b><i>RPGRIP1</i>.</b> 4.5% (8/179)</div></li><li class="half_rhythm"><div><b><i>AIPL1</i>.</b> 3.4% (6/179)</div></li><li class="half_rhythm"><div><b><i>TULP1</i>.</b> 1.7% (3/179)</div></li><li class="half_rhythm"><div><b><i>CRX</i>.</b> 0.6% (1/179)</div></li></ul><p>The authors found that the presence of photophobia or night blindness at ages one and two years distinguished two groups:</p><ul><li class="half_rhythm"><div>Those with photophobia constituted a cone-rod dystrophy class and were found to have pathogenic variants of <i>GUCY2D</i>, <i>RPGRIP1</i>, and <i>AIPL1.</i></div></li><li class="half_rhythm"><div>Those with night blindness constituted a rod-cone dystrophy class and were found to have pathogenic variants of <i>CRB1</i>, <i>RPE65</i>, <i>TULP1</i>, and <i>CRX.</i></div></li></ul></div><div id="lca.Prevalence"><h3>Prevalence</h3><p>The birth prevalence of LCA is two to three per 100,000 births. The condition is the most common cause of inherited blindness in childhood and constitutes more than 5% of all retinal dystrophies. LCA accounts for the cause of blindness in more than 20% of children attending schools for the blind.</p><p>LCA appears to be more prevalent when consanguinity is common [<a class="bibr" href="#lca.REF.sitorus.2003.1065" rid="lca.REF.sitorus.2003.1065">Sitorus et al 2003</a>].</p></div></div><div id="lca.Genetically_Related_Allelic_Disorder"><h2 id="_lca_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>Different pathogenic variants within each of the LCA-associated genes are known to cause other retinal dystrophies, such as <a href="/books/n/gene/rp-overview/?report=reader">retinitis pigmentosa</a> (RP) and cone-rod dystrophy. Sequence changes that cause LCA have therefore been considered to be at the severe end of the spectrum of retinal abnormalities and are presumed to render the protein product non-functional or absent:</p><ul><li class="half_rhythm"><div><b><i>GUCY2D</i> (LCA1).</b> Pathogenic variants also cause autosomal dominant cone-rod dystrophy 6.</div></li><li class="half_rhythm"><div><b><i>RPE65</i> (LCA2).</b> Pathogenic variants also cause autosomal recessive RP, or an attenuated form of LCA with better visual function [<a class="bibr" href="#lca.REF.morimura.1998.3088" rid="lca.REF.morimura.1998.3088">Morimura et al 1998</a>, <a class="bibr" href="#lca.REF.lorenz.2008.5235" rid="lca.REF.lorenz.2008.5235">Lorenz et al 2008</a>].</div></li><li class="half_rhythm"><div><b><i>AIPL1</i> (LCA4).</b> Pathogenic variants also cause autosomal dominant cone-rod dystrophy and autosomal dominant juvenile RP [<a class="bibr" href="#lca.REF.sohocki.2000.79" rid="lca.REF.sohocki.2000.79">Sohocki et al 2000</a>].</div></li><li class="half_rhythm"><div><b><i>RPGRIP1</i></b>
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<b>(LCA6).</b> Specific pathogenic variants (<a href="/books/NBK1298/table/lca.T.rpgrip1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figoblcaTrpgrip1pathogenicvariantsdiscus">p.Arg827Leu</a> and <a href="/books/NBK1298/table/lca.T.rpgrip1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figoblcaTrpgrip1pathogenicvariantsdiscus">p.Ala547Ser</a>) have been reported to cause autosomal recessive cone-rod dystrophy-13 (CORD13) in four consanguineous Pakistani families [<a class="bibr" href="#lca.REF.hameed.2003.616" rid="lca.REF.hameed.2003.616">Hameed et al 2003</a>].</div></li><li class="half_rhythm"><div><b><i>CRX</i> (LCA7).</b> Pathogenic variants also cause autosomal dominant cone-rod dystrophy-2 (CORD2), autosomal dominant RP, and autosomal dominant LCA [<a class="bibr" href="#lca.REF.lotery.2000.538" rid="lca.REF.lotery.2000.538">Lotery et al 2000</a>]. <i>De novo</i> dominant pathogenic variants of <i>CRX</i> have been recognized [<a class="bibr" href="#lca.REF.perrault.2003.e90" rid="lca.REF.perrault.2003.e90">Perrault et al 2003</a>].</div></li><li class="half_rhythm"><div><b><i>CRB1</i></b>
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<b>(LCA8)<i>.</i></b> Pathogenic variants also cause autosomal dominant pigmented paravenous chorioretinal atrophy and autosomal recessive retinitis pigmentosa. The most common allele, <a href="/books/NBK1298/table/lca.T.crb1_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrb1pathogenicvariantsdiscussed">p.Cys948Tyr</a>, is found in the homozygous state only in individuals with LCA [<a class="bibr" href="#lca.REF.den_hollander.2001.198" rid="lca.REF.den_hollander.2001.198">den Hollander et al 2001</a>, <a class="bibr" href="#lca.REF.lotery.2001.415" rid="lca.REF.lotery.2001.415">Lotery et al 2001</a>]. Individuals with compound heterozygosity for the p.Cys948Tyr allele and a "milder" missense variant on the other allele have RP [<a class="bibr" href="#lca.REF.den_hollander.2001.198" rid="lca.REF.den_hollander.2001.198">den Hollander et al 2001</a>]. Less deleterious pathogenic variants of <i>CRB1</i> cause RP, RP with Coats-like vasculopathy, and RP with preserved para-arteriolar RPE (PPRPE) [<a class="bibr" href="#lca.REF.den_hollander.1999.217" rid="lca.REF.den_hollander.1999.217">den Hollander et al 1999</a>].</div></li><li class="half_rhythm"><div><b><i>CEP290</i> (LCA10).</b> Pathogenic variants also cause a number of syndromic phenotypes (often involving abnormalities of the retina):</div><ul><li class="half_rhythm"><div><a href="/books/n/gene/bbs/?report=reader">Bardet-Biedl syndrome</a> 14; an autosomal recessive condition characterized by rod-cone dystrophy, obesity, polydactyly, cognitive impairment, genitourinary and renal abnormalities.</div></li><li class="half_rhythm"><div><a href="/books/n/gene/joubert/?report=reader">Joubert syndrome</a> 5; an autosomal recessive condition characterized by brain abnormalities, hypotonia, developmental delays, and early onset retinal dystrophy.</div></li><li class="half_rhythm"><div>Meckel syndrome 4; an autosomal recessive condition characterized by renal cysts, CNS anomalies, hepatic abnormalities, and polydactyly.</div></li><li class="half_rhythm"><div>Senior-Løken syndrome 6; an autosomal recessive condition characterized by nephronophthisis and Leber congenital amaurosis.</div></li><li class="half_rhythm"><div><a href="/books/n/gene/nephron-ov/?report=reader">Nephronophthisis</a> (NPHP), which manifests initially as a urine-concentrating defect and anemia before progressing to end-stage renal disease (ESRD) in childhood in most individuals [<a class="bibr" href="#lca.REF.hildebrandt.2007.1855" rid="lca.REF.hildebrandt.2007.1855">Hildebrandt & Zhou 2007</a>, <a class="bibr" href="#lca.REF.otto.2008.418" rid="lca.REF.otto.2008.418">Otto et al 2008</a>, <a class="bibr" href="#lca.REF.salomon.2009.2333" rid="lca.REF.salomon.2009.2333">Salomon et al 2009</a>]. Renal ultrasound examination shows normal-size or small kidneys with increased echogenicity. Approximately 10%-20% of individuals with NPHP have central nervous system and/or ocular involvement that includes structural cerebellar and midbrain abnormalities overlapping with Joubert syndrome and related disorders (JSRD) and retinal degeneration (Senior-Løken syndrome). Locus name is NPHP6 (SLSN6).</div></li></ul></li><li class="half_rhythm"><div><b><i>IMPDH1</i> (LCA11).</b> Pathogenic variants are also associated with autosomal dominant RP.</div></li><li class="half_rhythm"><div><b><i>RDH12</i> (LCA13).</b> In their series of unrelated individuals with LCA, <a class="bibr" href="#lca.REF.perrault.2004.639" rid="lca.REF.perrault.2004.639">Perrault et al [2004]</a> identified <i>RDH12</i> pathogenic variants only in individuals affected with "congenital severe yet progressive rod-cone dystrophy." In contrast, <a class="bibr" href="#lca.REF.janecke.2004.850" rid="lca.REF.janecke.2004.850">Janecke et al [2004]</a> described three consanguineous Austrian kindreds with onset between ages two and four years, severe retinal dystrophy affecting both rods and cones, and progression to legal blindness between ages 18 and 25 years. The ERG was "extinguished" at the first investigation, as early as age five years.</div></li><li class="half_rhythm"><div><b><i>TULP1</i> (LCA15).</b> Pathogenic variants also cause autosomal recessive RP.</div></li><li class="half_rhythm"><div><b><i>KCNJ13</i></b>
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<b>(LCA16).</b> Pathogenic variants also cause snowflake vitreoretinal degeneration.</div></li><li class="half_rhythm"><div><b><i>IQCB1</i>.</b> Pathogenic variants also cause Senior-Løken syndrome-1; an autosomal recessive condition characterized by nephronophthisis and Leber congenital amaurosis.</div></li></ul></div><div id="lca.Differential_Diagnosis"><h2 id="_lca_Differential_Diagnosis_">Differential Diagnosis</h2><p>Leber congenital amaurosis (LCA) typically presents as an isolated ocular anomaly without systemic involvement. Occasionally, the same or similar retinal findings can be seen as part of a systemic disorder. Systemic abnormalities including renal anomalies, deafness, skeletal abnormalities, microcephaly, neurodevelopmental delay, intellectual disability, or oculomotor apraxia should alert the clinician to consider syndromic disorders associated with early-onset retinal dystrophy. Systemic disorders to consider include the following:</p><p><b>Senior-Løken syndrome</b> (OMIM <a href="https://omim.org/entry/266900" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">266900</a>) comprises:</p><ul><li class="half_rhythm"><div>Juvenile nephronophthisis (medullary cystic renal disease) and</div></li><li class="half_rhythm"><div>Early-onset retinal dystrophy.</div></li></ul><p>See <a href="/books/n/gene/nephron-ov/?report=reader">Nephronophthisis</a>.</p><p><b>Conorenal syndrome</b> (OMIM <a href="https://omim.org/entry/266920" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">266920</a>) comprises:</p><ul><li class="half_rhythm"><div>Cone-shaped digital epiphyses,</div></li><li class="half_rhythm"><div>Cerebellar hypoplasia, and</div></li><li class="half_rhythm"><div>Early-onset retinal dystrophy.</div></li></ul><p><a href="/books/n/gene/joubert/?report=reader"><b>Joubert syndrome</b></a> comprises:</p><ul><li class="half_rhythm"><div>Nephronophthisis (a juvenile-onset cystic kidney disease),</div></li><li class="half_rhythm"><div>Hypoplasia of the cerebellar vermis,</div></li><li class="half_rhythm"><div>Early-onset retinal dystrophy, and</div></li><li class="half_rhythm"><div>Either or both of the following:</div><ul><li class="half_rhythm"><div>Episodic hyperpnea and/or apnea</div></li><li class="half_rhythm"><div>Atypical eye movements</div></li></ul></li></ul><p><a href="/books/n/gene/pbd/?report=reader"><b>Peroxisomal biogenesis disorders, Zellweger syndrome spectrum</b></a> is a continuum of three phenotypes described before the biochemical and molecular bases of the disorders were known:</p><ul><li class="half_rhythm"><div>Zellweger syndrome (ZS) (OMIM <a href="https://omim.org/entry/214100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">214100</a>)</div></li><li class="half_rhythm"><div>Neonatal adrenoleukodystrophy (NALD) (OMIM <a href="https://omim.org/entry/202370" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">202370</a>)</div></li><li class="half_rhythm"><div>Infantile Refsum disease (IRD) (OMIM <a href="https://omim.org/entry/266510" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">266510</a>)</div></li></ul><p>ZS is the most severe and IRD the least severe. Children with ZS have retinal dystrophy, sensorineural hearing loss, developmental delay with hypotonia, and liver dysfunction; they usually die during the first year of life. The clinical courses of NALD and IRD are variable. Retinal degeneration is associated with congenital, liver, and renal abnormalities.</p><p><b>Infantile</b>
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<b>neuronal ceroid-lipofuscinosis</b>
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<b>(Santavuori-Haltia disease) (CLN1).</b> Affected children are normal at birth but develop retinal vision impairment, loss of milestones, and progressive microcephaly by age six to 12 months. Virtual blindness ensues by age two years, seizures and progressive mental deterioration develop, and death generally occurs between ages three and 11 years [<a class="bibr" href="#lca.REF.weleber.1998.580" rid="lca.REF.weleber.1998.580">Weleber 1998</a>]. Affected children have characteristic electronegative electroretinograms early in the course of disease [<a class="bibr" href="#lca.REF.weleber.2004.128" rid="lca.REF.weleber.2004.128">Weleber et al 2004</a>]. The diagnosis can be established by assay of the enzyme palmitoyl-protein thioesterase 1 (PPT1), and/or identification of the causative variants within <i>CLN1</i>, the gene encoding PPT1.</p><p>
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<b>Other</b>
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</p><ul><li class="half_rhythm"><div>In addition, an LCA-like retinal dystrophy has been documented in individuals with abetalipoproteinemia (OMIM <a href="https://omim.org/entry/200100" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">200100</a>), hyperthreoninemia (OMIM <a href="https://omim.org/entry/273770" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">273770</a>), and disorders of mitochondrial dysfunction (see <a href="/books/n/gene/mt-overview/?report=reader">Mitochondrial Disorders Overview</a>). Common clinical features of mitochondrial disease include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. The central nervous system findings are often fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity.</div></li><li class="half_rhythm"><div><b><i>CABP4</i></b> pathogenic variants most often cause autosomal recessive congenital stationary night blindness, CSNB2. <i>CABP4,</i> located at 11q13.1, encodes calcium-binding protein 4, which plays a role in bipolar cell signaling. Calcium-binding protein 4 is localized intracellularly to the synaptic terminals of photoreceptors and is essential for neurotransmission to the bipolar cells. Loss of function results in three seemingly distinct phenotypes—autosomal congenital stationary night blindness (CSNB2), associated with alleles c.370C>T (p.Arg124Cys) and c.800_801delAG (p.Glu267fsTer91) [<a class="bibr" href="#lca.REF.zeitz.2006.657" rid="lca.REF.zeitz.2006.657">Zeitz et al 2006</a>], a cone-rod dystrophy associated with c.646C>T (p.Arg216Ter) [<a class="bibr" href="#lca.REF.littink.2009" rid="lca.REF.littink.2009">Littink et al 2009</a>], and Leber congenital amaurosis in a single Bedouin family associated with c.81_82insA (p.Pro28ThrfsTer44) in a homozygous state. This variant is considered a true null allele [<a class="bibr" href="#lca.REF.aldahmesh.2010.207" rid="lca.REF.aldahmesh.2010.207">Aldahmesh et al 2010</a>].</div></li><li class="half_rhythm"><div>In a child presenting without systemic involvement, other inherited retinal dystrophies may be considered. Compared to LCA, early-onset <a href="/books/n/gene/rp-overview/?report=reader">retinitis pigmentosa</a> (RP) has a later age of onset, better preservation of central visual acuity, and no nystagmus. The electroretinogram (ERG) is useful in distinguishing between LCA and RP: in the early stages of RP, the photopic component of the ERG typically shows some degree of sparing, while in LCA both the photopic and scotopic ERG are profoundly abnormal.</div></li><li class="half_rhythm"><div>An intermediate category of retinal disease, presenting in early childhood with night blindness, variable degrees of central vision loss, and a severely abnormal but recordable ERG is now emerging. The authors favor the term "SECORD" (<i>s</i>evere <i>e</i>arly-<i>c</i>hildhood <i>o</i>nset <i>r</i>etinal <i>d</i>ystrophy) to describe this entity, although terms such as early-onset severe retinal dystrophy (EOSRD) and early-onset severe RP have been variably used in the literature. SECORD is distinguished from LCA primarily by the age of onset and severity: the diagnosis of LCA should be reserved for infants presenting before age one year with nystagmus, severely impaired vision, and an unrecordable or nearly unrecordable ERG.</div></li><li class="half_rhythm"><div>Other retinal conditions that can be confused with Leber congenital amaurosis include congenital retinal disorders that are typically stationary, such as <a href="/books/n/gene/achm/?report=reader">achromatopsia</a> and <a href="/books/n/gene/csnb/?report=reader">congenital stationary night-blindness</a>, which can usually be easily distinguished by characteristic patterns of electroretinographic abnormality. However, rare combinations of mutated alleles for these disorders can lead to progressive disease.</div></li></ul></div><div id="lca.Management"><h2 id="_lca_Management_">Management</h2><div id="lca.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease in an individual diagnosed with Leber congenital amaurosis (LCA), the following evaluations are recommended:</p><ul><li class="half_rhythm"><div>Electroretinogram (ERG) to confirm the diagnosis and to assess retinal function</div></li><li class="half_rhythm"><div>Clinical genetic assessment to evaluate for the presence of systemic abnormalities</div></li><li class="half_rhythm"><div>Clinical genetics consultation</div></li></ul></div><div id="lca.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Except for <i>RPE65</i>-related LCA (see <a href="#lca.Therapies_Under_Investigation">Therapies Under Investigation</a>), no substantial treatment or cure for LCA exists, and, thus, care is supportive. Parents should be referred to programs for the visually impaired child within their state or locality.</p><p>Affected individuals benefit from correction of refractive error, use of low-vision aids when possible, and optimal access to educational and work-related opportunities.</p></div><div id="lca.Prevention_of_Secondary_Complication"><h3>Prevention of Secondary Complications</h3><p>Children should be discouraged from repeatedly poking and pressing on their eyes, although attempts to alter such behavior are not always successful.</p></div><div id="lca.Surveillance"><h3>Surveillance</h3><p>Affected individuals should be periodically seen for assessment of vision, trials of correction for refractive error, and when residual vision is present, assessment of the presence of amblyopia, glaucoma, or cataract.</p><p>Rarely, vision appears to improve beyond expectations; in such cases, a repeat ERG is indicated.</p></div><div id="lca.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>See <a href="#lca.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="lca.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><p>In a naturally occurring Briard dog model of LCA resulting from mutation of <i>RPE65</i>, gene therapy utilizing AAV-mediated <i>RPE65</i> was shown to restore visual function, an effect that has been documented to last for more than five years [<a class="bibr" href="#lca.REF.acland.2005.1072" rid="lca.REF.acland.2005.1072">Acland et al 2005</a>]. More than 50 dogs have now been treated, with sustained success in 95% of treated eyes. The results of three simultaneous Phase I clinical treatment trials of AAV-mediated <i>RPE65</i> gene therapy in humans were recently reported [<a class="bibr" href="#lca.REF.bainbridge.2008.2231" rid="lca.REF.bainbridge.2008.2231">Bainbridge et al 2008</a>, <a class="bibr" href="#lca.REF.cideciyan.2008.15112" rid="lca.REF.cideciyan.2008.15112">Cideciyan et al 2008</a>, <a class="bibr" href="#lca.REF.hauswirth.2008.979" rid="lca.REF.hauswirth.2008.979">Hauswirth et al 2008</a>, <a class="bibr" href="#lca.REF.maguire.2008.2240" rid="lca.REF.maguire.2008.2240">Maguire et al 2008</a>]. Initial results demonstrated safety, and showed slight improvement in vision in both bright and dim light.</p><p>Clinical and laboratory studies suggest that persons with <i>CEP290</i>-related LCA may also be good candidates for gene therapy. <a class="bibr" href="#lca.REF.cideciyan.2008.15112" rid="lca.REF.cideciyan.2008.15112">Cideciyan et al [2008]</a> studied the retinal architecture of <i>CEP290</i>-mutant mice and humans. In the mouse retina, dramatic retinal remodeling was evident by age four to six weeks. Cross-sectional imaging of affected human retinas performed using optical coherence tomography (OCT) indicated preservation of foveal cones. The relative sparing of foveal cone cells, despite severe visual dysfunction, suggests an opportunity for cell rescue.</p><p>Search <a href="https://clinicaltrials.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ClinicalTrials.gov</a> in the US and <a href="https://www.clinicaltrialsregister.eu/ctr-search/search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">EU Clinical Trials Register</a> in Europe for access to information on clinical studies for a wide range of diseases and conditions.</p></div></div><div id="lca.Genetic_Counseling"><h2 id="_lca_Genetic_Counseling_">Genetic Counseling</h2><p>
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<i>Genetic counseling is the process of providing individuals and families with
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information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them
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make informed medical and personal decisions. The following section deals with genetic
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risk assessment and the use of family history and genetic testing to clarify genetic
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status for family members; it is not meant to address all personal, cultural, or
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ethical issues that may arise or to substitute for consultation with a genetics
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professional</i>. —ED.</p><div id="lca.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Most often, Leber congenital amaurosis (LCA) is inherited in an autosomal recessive manner. Rarely, pathogenic variants in <i>CRX</i> causing LCA are inherited in an autosomal dominant manner.</p></div><div id="lca.Autosomal_Recessive_LCA__Risk_to_Fam"><h3>Autosomal Recessive LCA – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>The parents of an affected child are obligate heterozygotes and therefore carry one mutated allele.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic.</div></li></ul><p>
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<b>Sibs of a proband</b>
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</p><ul><li class="half_rhythm"><div>At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.</div></li><li class="half_rhythm"><div>Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.</div></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic.</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with Leber congenital amaurosis are obligate heterozygotes (carriers) for a pathogenic variant.</p><p><b>Other family members of a proband.</b> Sibs of the proband's parents are at a 50% risk of being carriers.</p><div id="lca.Carrier_Detection"><h4>Carrier Detection</h4><p>Carrier testing for at-risk family members is possible if the pathogenic variants in the family are known.</p></div></div><div id="lca.Autosomal_Dominant_LCA__Risk_to_Fami"><h3>Autosomal Dominant LCA – Risk to Family Members</h3><p>
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<b>Parents of a proband</b>
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</p><ul><li class="half_rhythm"><div>Most children diagnosed as having autosomal dominant LCA have an affected parent.</div></li><li class="half_rhythm"><div>Occasionally a molecular diagnosis is made in the absence of family history. Such cases are the result of <i>de novo</i> pathogenic variants in <i>CRX</i> [<a class="bibr" href="#lca.REF.jacobson.1998.2417" rid="lca.REF.jacobson.1998.2417">Jacobson et al 1998</a>, <a class="bibr" href="#lca.REF.sohocki.1998.1307" rid="lca.REF.sohocki.1998.1307">Sohocki et al 1998</a>, <a class="bibr" href="#lca.REF.swaroop.1999.299" rid="lca.REF.swaroop.1999.299">Swaroop et al 1999</a>, <a class="bibr" href="#lca.REF.rivolta.2001.488" rid="lca.REF.rivolta.2001.488">Rivolta et al 2001</a>, <a class="bibr" href="#lca.REF.perrault.2003.e90" rid="lca.REF.perrault.2003.e90">Perrault et al 2003</a>].</div></li></ul><p><b>Sibs of a proband.</b> The risk to sibs depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If one of the proband's parents is affected with LCA, the risk to sibs of inheriting the mutated allele is 50%.</div></li><li class="half_rhythm"><div>When neither parent of the proband is affected, the risk to sibs is negligible.</div></li></ul><p><b>Offspring of a proband.</b> Individuals with autosomal dominant LCA have a 50% chance of transmitting the mutated allele to each child.</p><p><b>Other family members of a proband.</b> The risk to other family members depends on the status of the proband's parents: if a parent is affected, his or her family members are at risk.</p></div><div id="lca.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>
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<b>Family planning</b>
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</p><ul><li class="half_rhythm"><div>The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking</b> is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.</p></div><div id="lca.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for Leber congenital amaurosis are possible.</p></div></div><div id="lca.Resources"><h2 id="_lca_Resources_">Resources</h2><p>
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<i>GeneReviews staff has selected the following disease-specific and/or umbrella
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support organizations and/or registries for the benefit of individuals with this disorder
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and their families. GeneReviews is not responsible for the information provided by other
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organizations. For information on selection criteria, click <a href="/books/n/gene/app4/?report=reader">here</a>.</i></p>
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<ul><li class="half_rhythm"><div>
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<b>American Council of the Blind (ACB)</b>
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</div><div>2200 Wilson Boulevard</div><div>Suite 650</div><div>Arlington VA 22201</div><div><b>Phone:</b> 800-424-8666 (toll-free); 202-467-5081</div><div><b>Fax:</b> 202-467-5085</div><div><b>Email:</b> info@acb.org</div><div>
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<a href="http://www.acb.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.acb.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Foundation Fighting Blindness</b>
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</div><div>11435 Cronhill Drive</div><div>Owings Mills MD 21117-2220</div><div><b>Phone:</b> 800-683-5555 (toll-free); 800-683-5551 (toll-free TDD); 410-568-0150</div><div><b>Email:</b> info@fightblindness.org</div><div>
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<a href="http://www.blindness.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.blindness.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Federation of the Blind (NFB)</b>
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</div><div>200 East Wells Street</div><div>(at Jernigan Place)</div><div>Baltimore MD 21230</div><div><b>Phone:</b> 410-659-9314</div><div><b>Fax:</b> 410-685-5653</div><div><b>Email:</b> pmaurer@nfb.org</div><div>
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<a href="http://www.nfb.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.nfb.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Retina International</b>
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</div><div>Retina Suisse</div><div>Ausstellungsstrasse 36</div><div> Zurich CH-8005</div><div>Switzerland</div><div><b>Phone:</b> +41 (0) 44 444 1077</div><div><b>Fax:</b> +41 (0) 44 444 1070</div><div><b>Email:</b> christina.fasser@retina-international.org</div><div>
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<a href="http://www.retina-international.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.retina-international.org</a>
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</div></li></ul>
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</div><div id="lca.Molecular_Genetics"><h2 id="_lca_Molecular_Genetics_">Molecular Genetics</h2><p><i>Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —</i>ED.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcamolgenTA"><a href="/books/NBK1298/table/lca.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figoblcamolgenTA"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.molgen.TA"><a href="/books/NBK1298/table/lca.molgen.TA/?report=objectonly" target="object" rid-ob="figoblcamolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Leber Congenital Amaurosis: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcamolgenTB"><a href="/books/NBK1298/table/lca.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figoblcamolgenTB"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.molgen.TB"><a href="/books/NBK1298/table/lca.molgen.TB/?report=objectonly" target="object" rid-ob="figoblcamolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Leber Congenital Amaurosis (View All in OMIM) </p></div></div><p>
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<b><i>GUCY2D</i> (LCA1)</b>
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</p><p><b>Gene structure.</b>
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<i>GUCY2D</i> has 20 exons.</p><p><b>Pathogenic variants.</b> See <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTgucy2dpathogenicvariantsdiscuss"><a href="/books/NBK1298/table/lca.T.gucy2d_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figoblcaTgucy2dpathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.gucy2d_pathogenic_variants_discuss"><a href="/books/NBK1298/table/lca.T.gucy2d_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTgucy2dpathogenicvariantsdiscuss">Table 2. </a></h4><p class="float-caption no_bottom_margin"><i>GUCY2D</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> Retinal guanylyl cyclase 1 (retGC-1), a transmembrane protein located in the photoreceptor outer segments, is critical in the recovery process of the phototransduction cascade.</p><p><b>Abnormal gene product.</b> Most pathogenic variants result in, or predict, truncation of the protein and complete loss of function. Complete loss of function of retGC-1 catalytic activity from pathogenic variants in <i>GUCY2D</i> consistently results in LCA [<a class="bibr" href="#lca.REF.rozet.2001.1190" rid="lca.REF.rozet.2001.1190">Rozet et al 2001</a>]. Pathologic study of the eyes of a 33-week aborted fetus disclosed cell loss of the outer nuclear layer, decreased immunolabeling of phototransduction proteins, and aberrant synaptic and inner retinal organization, suggesting that pathophysiologic events are well established prior to birth [<a class="bibr" href="#lca.REF.porto.2002.390" rid="lca.REF.porto.2002.390">Porto et al 2002</a>]. Clinicopathologic correlation in an 11½-year-old affected subject disclosed retention of substantial numbers of cones and rods in the macula and far periphery, portending well for therapeutic intervention at this age [<a class="bibr" href="#lca.REF.milam.2003.549" rid="lca.REF.milam.2003.549">Milam et al 2003</a>].</p><p>
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<b><i>RPE65</i> (LCA2)</b>
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</p><p><b>Gene structure.</b>
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<i>RPE65</i> has 14 exons.</p><p><b>Pathogenic variants.</b> See <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><p><b>Normal gene product.</b> Retinal pigment epithelium-specific 65-kd protein forms a complex with LRAT to act as the isomerolhydrolase in the regeneration of the visual pigment, vitamin A [<a class="bibr" href="#lca.REF.redmond.2005.13658" rid="lca.REF.redmond.2005.13658">Redmond et al 2005</a>].</p><p><b>Abnormal gene product.</b> In the absence of the protein encoded for by <i>RPE65</i>, isomerization of all-trans retinal to 11<i>-cis</i> retinal in the retinal pigment epithelium is inhibited.</p><p>
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<b><i>SPATA7</i> (LCA3)</b>
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</p><p><b>Gene structure.</b>
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<i>SPATA7</i> has at least 12 exons.</p><p><b>Pathogenic variants.</b>
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<a class="bibr" href="#lca.REF.wang.2009.380" rid="lca.REF.wang.2009.380">Wang et al [2009]</a> found a homozygous 322C>T transition in exon 5 that resulted in a (p.Arg108Ter) substitution that segregated with disease in a Saudi Arabian family and was present also in a Dutch patient with LCA. Other sequence changes include homozygosity for different truncating variants: c.1183C>T transition in exon 11, resulting in an p.Arg395Ter substitution, and 1-bp duplication (c.960dupA) in exon 8, resulting in a frameshift. LCA with a more severe phenotype was seen with nonsense variants involving the middle of the <i>SPATA7</i> coding region, whereas homozygosity for pathogenic variants in the last two exons of <i>SPATA7</i> – including the p.Arg395Ter in exon 11 and a 1-bp deletion (c.1395delA) in exon 12 — were associated with juvenile RP. See <a href="/books/NBK1298/table/lca.T.spata7_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTspata7pathogenicvariantsdiscuss">Table 3</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTspata7pathogenicvariantsdiscuss"><a href="/books/NBK1298/table/lca.T.spata7_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figoblcaTspata7pathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.spata7_pathogenic_variants_discuss"><a href="/books/NBK1298/table/lca.T.spata7_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTspata7pathogenicvariantsdiscuss">Table 3. </a></h4><p class="float-caption no_bottom_margin"><i>SPATA7</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> The gene encodes a 599-amino acid protein that includes several DNA-binding sites and three phosphorylation sites. Human and rat protein have 77% sequence identity. Expression in mouse is in the testis, where it localizes to primary spermatocytes, and in several layers of the retina.</p><p><b>Abnormal gene product.</b> How the abnormal gene product results in disease is not known.</p><p>
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<b><i>AIPL1</i> (LCA4)</b>
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</p><p><b>Gene structure.</b>
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<i>AIPL1</i> has six exons.</p><p><b>Pathogenic variants.</b> The majority of pathogenic variants result in a null genotype. The most frequent allele, p.Trp278Ter, probably represents a founder effect in the Pakistani population. See <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTaipl1pathogenicvariantsdiscusse"><a href="/books/NBK1298/table/lca.T.aipl1_pathogenic_variants_discusse/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figoblcaTaipl1pathogenicvariantsdiscusse"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.aipl1_pathogenic_variants_discusse"><a href="/books/NBK1298/table/lca.T.aipl1_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figoblcaTaipl1pathogenicvariantsdiscusse">Table 4. </a></h4><p class="float-caption no_bottom_margin"><i>AIPL1</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> The role of aryl-hydrocarbon interacting protein-like 1 (AIPL1) has yet to be defined, although it may act as a molecular chaperone. AIPL1 is expressed in adult retina only in rods, but expression coincides with both rod and cone photoreceptors during fetal development and AIPL1 may be essential for the normal development of both photoreceptor types [<a class="bibr" href="#lca.REF.van_der_spuy.2003.5396" rid="lca.REF.van_der_spuy.2003.5396">van der Spuy et al 2003</a>].</p><p><b>Abnormal gene product.</b> Certain pathogenic variants of <i>AIPL1</i> (p.Trp278Ter, p.Ala197Pro, p.Cys239Arg), but not others (e.g., p.Ile206Asn, p.Gly262Ser, p.Arg302Leu, p.Pro376Ser), abolish an interaction with NEDD8 ultimate buster-1 (encoded by <i>NUB1</i>), which is an inducible protein that recruits ubiquitin-like proteins to the proteasome for degradation [<a class="bibr" href="#lca.REF.kanaya.2004.768" rid="lca.REF.kanaya.2004.768">Kanaya et al 2004</a>]. The loss of the AIPL1 binding site that supports this interaction has been suggested to contribute to the pathogenesis of LCA in these cases [<a class="bibr" href="#lca.REF.kanaya.2004.768" rid="lca.REF.kanaya.2004.768">Kanaya et al 2004</a>]. Clinicopathologic correlation of a 22-year-old subject with mutation of <i>AIPL1</i> and LCA demonstrated almost total loss of photoreceptors, retinal gliosis, decreased ganglion cells, increased vacuolizations of the nerve fiber layer, and unusual vascular morphology [<a class="bibr" href="#lca.REF.heegaard.2003.980" rid="lca.REF.heegaard.2003.980">Heegaard et al 2003</a>].</p><p>
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<b><i>LCA5</i> (LCA5)</b>
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</p><p><b>Gene structure.</b> The gene has nine exons.</p><p><b>Benign variants.</b>
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<i>LCA5</i> has two normal splice variants.</p><p><b>Pathogenic variants.</b>
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<a class="bibr" href="#lca.REF.den_hollander.2007.889" rid="lca.REF.den_hollander.2007.889">Den Hollander et al [2007]</a> reported three Pakistani families with a shared homozygous haplotype. These families had a homozygous c.1151delC pathogenic variant in exon 6 that results in a frameshift. Three other pathogenic variants were found—a homozygous 1-bp duplication (c.1476dupA) in exon 9, a homozygous c.835C>T transition in exon 5, and a 1,598-bp deletion that encompassed 1, 077 bp of the promoter region and non-coding exon 1 (g.(-19612)-(-18015)del1598) [<a class="bibr" href="#lca.REF.den_hollander.2007.889" rid="lca.REF.den_hollander.2007.889">den Hollander et al 2007</a>]. See <a href="/books/NBK1298/table/lca.T.lca5_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTlca5pathogenicvariantsdiscussed">Table 5</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTlca5pathogenicvariantsdiscussed"><a href="/books/NBK1298/table/lca.T.lca5_pathogenic_variants_discussed/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figoblcaTlca5pathogenicvariantsdiscussed"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.lca5_pathogenic_variants_discussed"><a href="/books/NBK1298/table/lca.T.lca5_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTlca5pathogenicvariantsdiscussed">Table 5. </a></h4><p class="float-caption no_bottom_margin"><i>LCA5</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> The normal gene product, lebercilin, is a 697-amino acid protein that contains four coiled-coil domains and is expressed in adult retina, testis, kidney, and heart, and in fetal eye, cochlea, and brain. In adult eye, the expression was limited to photoreceptors. In mouse and rat, lebercelin is localized to the ciliary axoneme in ciliated lines; in mouse and rat retina, it is located between outer and inner segments of the photoreceptor layer. In human kidney cells, lebercilin was found to interact with 24 ciliary body proteins, including cytoplasmic dynein, nucleophosmin, nucleolin, 14-3-3-epsilon, and HSP70. Thus, lebercilin appears to play a role in ciliary function.</p><p><b>Abnormal gene product.</b> The precise nature of the effect of mutation on gene function is unknown.</p><p>
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<b><i>RPGRIP1</i> (LCA6)</b>
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</p><p><b>Gene structure.</b>
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<i>RPGRIP1</i> has 24 exons.</p><p><b>Pathogenic variants.</b> See <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTrpgrip1pathogenicvariantsdiscus"><a href="/books/NBK1298/table/lca.T.rpgrip1_pathogenic_variants_discus/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figoblcaTrpgrip1pathogenicvariantsdiscus"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.rpgrip1_pathogenic_variants_discus"><a href="/books/NBK1298/table/lca.T.rpgrip1_pathogenic_variants_discus/?report=objectonly" target="object" rid-ob="figoblcaTrpgrip1pathogenicvariantsdiscus">Table 6. </a></h4><p class="float-caption no_bottom_margin"><i>RPGRIP1</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> Expression of X-linked retinitis pigmentosa GTPase regulator (RPGR)-interacting protein-1 is confined to the rod and cone retinal photoreceptor, where it localizes to the connecting cilium, is presumed to anchor RPGR in the photoreceptor cilium, and appears to be required for disk morphogenesis, putatively by regulating actin cytoskeleton dynamics [<a class="bibr" href="#lca.REF.zhao.2003.3965" rid="lca.REF.zhao.2003.3965">Zhao et al 2003</a>].</p><p><b>Abnormal gene product.</b> Most pathogenic variants result in truncation of the protein and complete loss of function.</p><p>
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<b><i>CRX</i> (LCA7)</b>
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</p><p><b>Gene structure.</b>
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<i>CRX</i> has three exons.</p><p><b>Pathogenic variants.</b> See <a href="/books/NBK1298/table/lca.T.crx_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrxpathogenicvariantsdiscussed">Table 7</a>, <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTcrxpathogenicvariantsdiscussed"><a href="/books/NBK1298/table/lca.T.crx_pathogenic_variants_discussed/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figoblcaTcrxpathogenicvariantsdiscussed"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.crx_pathogenic_variants_discussed"><a href="/books/NBK1298/table/lca.T.crx_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrxpathogenicvariantsdiscussed">Table 7. </a></h4><p class="float-caption no_bottom_margin"><i>CRX</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> Cone-rod homeobox protein is a transcription factor essential for the elongation of photoreceptor outer segments and the phototransduction cascade.</p><p><b>Abnormal gene product.</b> The C-terminal region of <i>CRX</i>, between amino acids 200 and 284, is essential for CRX-mediated transcriptional activation. <i>CRX</i> pathogenic variants may lead to human photoreceptor degeneration by impairing <i>CRX</i>-mediated transcriptional regulation of the photoreceptor genes [<a class="bibr" href="#lca.REF.chen.2002.873" rid="lca.REF.chen.2002.873">Chen et al 2002</a>].</p><p>
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<b><i>CRB1</i> (LCA8)</b>
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</p><p><b>Gene structure.</b>
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<i>CRB1</i> has 12 exons.</p><p><b>Pathogenic variants.</b> The most common allele, observed in 20% of individuals with LCA, is <a href="/books/NBK1298/table/lca.T.crb1_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrb1pathogenicvariantsdiscussed">p.Cys948Tyr</a>. See <a href="/books/NBK1298/table/lca.T.crb1_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrb1pathogenicvariantsdiscussed">Table 8</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTcrb1pathogenicvariantsdiscussed"><a href="/books/NBK1298/table/lca.T.crb1_pathogenic_variants_discussed/?report=objectonly" target="object" title="Table 8. " class="img_link icnblk_img" rid-ob="figoblcaTcrb1pathogenicvariantsdiscussed"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.crb1_pathogenic_variants_discussed"><a href="/books/NBK1298/table/lca.T.crb1_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTcrb1pathogenicvariantsdiscussed">Table 8. </a></h4><p class="float-caption no_bottom_margin"><i>CRB1</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b>
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<i>CRB1</i> encodes a protein (protein crumbs homolog 1) thought to play a role in determining and maintaining photoreceptor architecture.</p><p><b>Abnormal gene product.</b> Mutated CRB1 protein may disturb the development of normal human retinal organization by interrupting naturally occurring apoptosis [<a class="bibr" href="#lca.REF.jacobson.2003.1073" rid="lca.REF.jacobson.2003.1073">Jacobson et al 2003</a>].</p><p>
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<b><i>NMNAT1</i> (LCA9)</b>
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</p><p><b>Gene structure.</b>
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<i>NMNAT1</i> has four exons. The LCA9 locus was associated originally with a single consanguineous Pakistani family with LCA. Four papers published in <i>Nature Genetics</i> 2012 report the discovery of <i>NMNAT1</i> as the gene in which mutation causes LCA9 [<a class="bibr" href="#lca.REF.chiang.2012.972" rid="lca.REF.chiang.2012.972">Chiang et al 2012</a>, <a class="bibr" href="#lca.REF.falk.2012.1040" rid="lca.REF.falk.2012.1040">Falk et al 2012</a>, <a class="bibr" href="#lca.REF.koenekoop.2012.1035" rid="lca.REF.koenekoop.2012.1035">Koenekoop et al 2012</a>, <a class="bibr" href="#lca.REF.perrault.2012.975" rid="lca.REF.perrault.2012.975">Perrault et al 2012</a>].</p><p><b>Pathogenic variants.</b> The most common allele in individuals with LCA9, observed with an allele frequency estimated at 0.001, is p.Glu257Lys [<a class="bibr" href="#lca.REF.chiang.2012.972" rid="lca.REF.chiang.2012.972">Chiang et al 2012</a>]. See <a href="/books/NBK1298/table/lca.T.nmnat1_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTnmnat1pathogenicvariantsdiscuss">Table 9</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTnmnat1pathogenicvariantsdiscuss"><a href="/books/NBK1298/table/lca.T.nmnat1_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 9. " class="img_link icnblk_img" rid-ob="figoblcaTnmnat1pathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.nmnat1_pathogenic_variants_discuss"><a href="/books/NBK1298/table/lca.T.nmnat1_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTnmnat1pathogenicvariantsdiscuss">Table 9. </a></h4><p class="float-caption no_bottom_margin"><i>NMNAT1</i> Pathogenic Variants Discussed in This GeneReview </p></div></div><p><b>Normal gene product.</b>
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<i>NMNAT1</i> encodes the nuclear isoform of nicotinamide mononucleotide adenylytransferase, which is the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD(+) biosynthesis [<a class="bibr" href="#lca.REF.emanuelli.2001.406" rid="lca.REF.emanuelli.2001.406">Emanuelli et al 2001</a>]. This enzyme is implicated in the protection against axonal degeneration [<a class="bibr" href="#lca.REF.araki.2004.1010" rid="lca.REF.araki.2004.1010">Araki et al 2004</a>].</p><p><b>Abnormal gene product.</b> Mutated <i>NMNAT1</i> protein disturbs enzymatic activity but the exact mechanism of disease within retinal cells has yet to be defined. [<a class="bibr" href="#lca.REF.falk.2012.1040" rid="lca.REF.falk.2012.1040">Falk et al 2012</a>].</p><p>
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<b><i>CEP290</i> (LCA10)</b>
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</p><p><b>Gene structure.</b>
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<i>CEP290</i> has 54 exons.</p><p><b>Pathogenic variants.</b> The most frequent sequence variant is <a href="/books/NBK1298/table/lca.T.cep290_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTcep290pathogenicvariantsdiscuss">c.2991+1655A>G</a>, an intronic donor splice site variant that inserts a cryptic exon in the <i>CEP290</i> messenger RNA. To date, all individuals with LCA resulting from <i>CEP290</i> have had at least one c.2991+1655A>G variant identified [<a class="bibr" href="#lca.REF.den_hollander.2006.556" rid="lca.REF.den_hollander.2006.556">den Hollander et al 2006</a>]. Heterozygous nonsense, frameshift, and splice site variants have been identified on the remaining allele.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTcep290pathogenicvariantsdiscuss"><a href="/books/NBK1298/table/lca.T.cep290_pathogenic_variants_discuss/?report=objectonly" target="object" title="Table 10. " class="img_link icnblk_img" rid-ob="figoblcaTcep290pathogenicvariantsdiscuss"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.cep290_pathogenic_variants_discuss"><a href="/books/NBK1298/table/lca.T.cep290_pathogenic_variants_discuss/?report=objectonly" target="object" rid-ob="figoblcaTcep290pathogenicvariantsdiscuss">Table 10. </a></h4><p class="float-caption no_bottom_margin"><i>CEP290</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> Centrosomal protein Cep290 (nephrocystin-6, NPHP6) is a centrosomal protein with probable ciliary function. The greatest concentration of NPHP6 occurs in the connecting cilium of mouse photoreceptor cells. NPHP6 putatively interacts with the protein retinitis pigmentosa GTPase regulator (RPGR), deficiency of which is the leading cause of X-linked <a href="/books/n/gene/rp-overview/?report=reader">retinitis pigmentosa</a> (RP), and nephrocystin-5, which is mutated in nephronophthisis type 5. NPHP6 also interacts with and activates ATF4-mediated transcription [<a class="bibr" href="#lca.REF.sayer.2006.674" rid="lca.REF.sayer.2006.674">Sayer et al 2006</a>].</p><p><b>Abnormal gene product.</b> Although the common <i>CEP290</i> c.2991+1655A>G pathogenic variant leads to aberrant splicing, early studies indicate that this pathogenic variant may allow low levels of nephrocystin-6 to remain intact. Den Hollander hypothesized that low residual nephrocystin-6 levels may be sufficient for normal cerebellar and renal function but insufficient for normal photoreceptor function [<a class="bibr" href="#lca.REF.den_hollander.2006.556" rid="lca.REF.den_hollander.2006.556">den Hollander et al 2006</a>]. Subsequent research reported by <a class="bibr" href="#lca.REF.perrault.2007.416" rid="lca.REF.perrault.2007.416">Perrault et al [2007]</a> challenges this hypothesis: in their series, nine patients with LCA were found to harbor two null alleles in <i>CEP290</i>. Of those, six had normal cognitive development and no evidence of the pathognomonic “molar tooth sign” indicative of Joubert syndrome on MRI.</p><p>
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<b><i>IMPDH1</i> (LCA11)</b>
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</p><p><b>Gene structure.</b>
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<i>IMPDH1</i> has 14 exons.</p><p><b>Pathogenic variants.</b> See <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><p><b>Normal gene product.</b>
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<i>IMPDH1</i> catalyzes the formation of xanthine monophosphate (XMP) from IMP. In the purine <i>de novo</i> synthetic pathway, IMP dehydrogenase is positioned at the branch point in the synthesis of adenine and guanine nucleotides and is thus the rate-limiting enzyme in the <i>de novo</i> synthesis of guanine nucleotides (OMIM <a href="http://omim.org/entry/146690" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">146690</a>).</p><p><b>Abnormal gene product.</b> Inhibition of cellular IMP dehydrogenase activity results in an abrupt cessation of DNA synthesis and a cell cycle block at the G1-S interface.</p><p>
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<b><i>RD3</i> (LCA12)</b>
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</p><p><b>Gene structure.</b> The gene contains at least three exons. Alternately spliced transcripts that lack exon 2 or are altered at the 5’ exons may exist.</p><p><b>Pathogenic variants.</b> In two sibs with LCA, <a class="bibr" href="#lca.REF.friedman.2006.1059" rid="lca.REF.friedman.2006.1059">Friedman et al [2006]</a> found a homozygous pathogenic variant <a href="/books/NBK1298/table/lca.T.rd3_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTrd3pathogenicvariantsdiscussed">c.296+1G>A</a> in the invariant G nucleotide of the <i>RD3</i> exon 2 donor splice site that would predict truncation of the protein.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTrd3pathogenicvariantsdiscussed"><a href="/books/NBK1298/table/lca.T.rd3_pathogenic_variants_discussed/?report=objectonly" target="object" title="Table 11. " class="img_link icnblk_img" rid-ob="figoblcaTrd3pathogenicvariantsdiscussed"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.rd3_pathogenic_variants_discussed"><a href="/books/NBK1298/table/lca.T.rd3_pathogenic_variants_discussed/?report=objectonly" target="object" rid-ob="figoblcaTrd3pathogenicvariantsdiscussed">Table 11. </a></h4><p class="float-caption no_bottom_margin"><i>RD3</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> The gene product is a 195-amino acid protein that contains an N-terminal mitochondrial targeting signal, a possible coiled-coil domain, and two potential phosphorylation sites. PCR analysis in human tissues detected expression only in retina. [<a class="bibr" href="#lca.REF.friedman.2006.1059" rid="lca.REF.friedman.2006.1059">Friedman et al 2006</a>] suggested that RD3 is part of a subnuclear protein involved in transcription and splicing.</p><p><b>Abnormal gene product.</b> Nothing definitive is known about the way pathogenic variants in this gene produce disease.</p><p>
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<b><i>RDH12</i> (LCA13)</b>
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</p><p><b>Gene structure.</b>
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<i>RDH12</i> has nine exons.</p><p><b>Pathogenic variants.</b> Pathogenic variants may be nonsense, missense, splice site, or frameshift. The most frequent sequence variant is p.Ala269GlyfsTer2, a frameshift deletion in exon 6 [<a class="bibr" href="#lca.REF.perrault.2004.639" rid="lca.REF.perrault.2004.639">Perrault et al 2004</a>]. See <a href="/books/NBK1298/table/lca.T.rdh12_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figoblcaTrdh12pathogenicvariantsdiscusse">Table 12</a>, <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figlcaTrdh12pathogenicvariantsdiscusse"><a href="/books/NBK1298/table/lca.T.rdh12_pathogenic_variants_discusse/?report=objectonly" target="object" title="Table 12. " class="img_link icnblk_img" rid-ob="figoblcaTrdh12pathogenicvariantsdiscusse"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="lca.T.rdh12_pathogenic_variants_discusse"><a href="/books/NBK1298/table/lca.T.rdh12_pathogenic_variants_discusse/?report=objectonly" target="object" rid-ob="figoblcaTrdh12pathogenicvariantsdiscusse">Table 12. </a></h4><p class="float-caption no_bottom_margin"><i>RDH12</i> Pathogenic Variants Discussed in This <i>GeneReview</i> </p></div></div><p><b>Normal gene product.</b> Retinol dehydrogenase 12 (RDH12) is a photoreceptor-specific enzyme involved in all-<i>trans</i>- and <i>cis</i>-retinol transformations, critical for the mediation of vision. RDH12 may be the key enzyme in the formation of 11-<i>cis</i>-retinal from 11-<i>cis</i>-retinol during regeneration of the cone visual pigments [<a class="bibr" href="#lca.REF.mcbee.2001.469" rid="lca.REF.mcbee.2001.469">McBee et al 2001</a>, <a class="bibr" href="#lca.REF.haeseleer.2002.45537" rid="lca.REF.haeseleer.2002.45537">Haeseleer et al 2002</a>].</p><p><b>Abnormal gene product.</b> Most <i>RDH12</i> pathogenic variants result in reduced expression and activity of the retinal dehydrogenase 12 enzyme, which disrupts the cycle of synthesis of the visual pigment chromophore, 11-<i>cis</i>-retinal, from 11-<i>trans</i>-retinal [<a class="bibr" href="#lca.REF.thompson.2005.3865" rid="lca.REF.thompson.2005.3865">Thompson et al 2005</a>].</p><p>
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<b><i>LRAT</i> (LCA14)</b>
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</p><p><b>Gene structure.</b>
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<i>LRAT</i> has three exons (<a href="/nuccore/NM_004744.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004744.3</a>).</p><p><b>Pathogenic variants.</b> Reported pathogenic variants include missense, splicing, small deletions, and small indels.</p><p><b>Normal gene product. .</b> The protein encoded by this gene has 230 amino acids and is a microsomal enzyme that catalyzes the esterification of all-trans-retinol into all-trans-retinyl ester, an essential reaction for the retinoid cycle in visual system and vitamin A status in liver. [provided by RefSeq, Jul 2008]</p><p><b>Abnormal gene product.</b> Pathogenic variants in this gene result in decreased enzymatic activity [<a class="bibr" href="#lca.REF.thompson.2001.123" rid="lca.REF.thompson.2001.123">Thompson et al 2001</a>]</p><p>
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<b><i>TULP1</i> (LCA15)</b>
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</p><p><b>Gene structure.</b>
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<i>TULP1</i> has 15 exons (<a href="/nuccore/NM_003322.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_003322.3</a>).</p><p><b>Pathogenic variants.</b> Reported pathogenic variants include missense, nonsense, splicing, small deletions, small insertions, and gross deletions.</p><p><b>Normal gene product.</b> The protein encoded by this gene has 542 amino acids and is a member of the tubby-like gene family (TULPs). It plays an important role in protein transport from the photoreceptor inner segment (IS) to the outer segment (OS) <i>TULP1</i> is expressed exclusively in photoreceptors.</p><p><b>Abnormal gene product.</b> Tulp1-/- mouse models suggest that mutation of this gene results in abnormal protein localization within the cell [<a class="bibr" href="#lca.REF.hagstrom.2012.783" rid="lca.REF.hagstrom.2012.783">Hagstrom et al 2012</a>].</p><p>
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<b><i>KCNJ13</i> (LCA16)</b>
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</p><p><b>Gene structure.</b>
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<i>KCNJ13</i> has three exons.</p><p><b>Pathogenic variants.</b> Missense and nonsense variants have been reported.</p><p><b>Normal gene product.</b> The protein encoded by this gene has 360 amino acids and is an inwardly rectifying potassium channel (where voltage dependence is regulated by the concentration of extracellular potassium) that functions as a homotetramer and is primarily localized to the apical membranes of RPE.</p><p><b>Abnormal gene product.</b> Some mutated alleles may lead to nonsense-mediated decay or prevent the formation of a functional homotetramer [<a class="bibr" href="#lca.REF.sergouniotis.2011.183" rid="lca.REF.sergouniotis.2011.183">Sergouniotis et al 2011</a>].</p><p>
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<b><i>IQCB1</i> (<i>NPHP5</i>)</b>
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</p><p><b>Gene structure.</b> This gene belongs to the ciliary body genome and is important for development and function of the retina and kidneys. The longest transcript variant <a href="/protein/NP_001018864.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001018864.2</a> has 15 exons.</p><p><b>Pathogenic variants.</b> Nonsense variants and small intragenic deletions have been reported.</p><p><b>Normal gene product:</b> The longest protein isoform (<a href="/protein/NP_001018864.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_001018864.2</a>) has 598 amino acids.</p><p><b>Abnormal gene product.</b> Nothing definitive is known about the way in which mutation of this gene produces disease.</p></div><div id="lca.References"><h2 id="_lca_References_">References</h2><div id="lca.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.acland.2005.1072">Acland GM, Aguirre GD, Bennett J, Aleman TS, Cideciyan AV, Bennicelli J, Dejneka NS, Pearce-Kelling SE, Maguire AM, Palczewski K, Hauswirth WW, Jacobson SG. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. <span><span class="ref-journal">Mol Ther. </span>2005;<span class="ref-vol">12</span>:1072–82.</span> [<a href="/pmc/articles/PMC3647373/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3647373</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16226919" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16226919</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.aldahmesh.2010.207">Aldahmesh MA, Al-Owain M, Alqahtani F, Hazzaa S, Alkuraya FS. 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Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. <span><span class="ref-journal">Am J Ophthalmol. </span>2007 Dec;<span class="ref-vol">144</span>:791–811.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17964524" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17964524</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.swaroop.1999.299">Swaroop A, Wang QL, Wu W, Cook J, Coats C, Xu S, Chen S, Zack DJ, Sieving PA. Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function. <span><span class="ref-journal">Hum Mol Genet. </span>1999;<span class="ref-vol">8</span>:299–305.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9931337" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9931337</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.thompson.2005.3865">Thompson DA, Janecke AR, Lange J, Feathers KL, Hubner CA, McHenry CL, Stockton DW, Rammesmayer G, Lupski JR, Antinolo G, Ayuso C, Baiget M, Gouras P, Heckenlively JR, den Hollander A, Jacobson SG, Lewis RA, Sieving PA, Wissinger B, Yzer S, Zrenner E, Utermann G, Gal A. Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle. <span><span class="ref-journal">Hum Mol Genet. </span>2005;<span class="ref-vol">14</span>:3865–75.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16269441" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16269441</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.thompson.2001.123">Thompson DA, Li Y, McHenry CL, Carlson TJ, Ding X, Sieving PA, Apfelstedt-Sylla E, Gal A. Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy. <span><span class="ref-journal">Nat Genet. </span>2001;<span class="ref-vol">28</span>:123–4.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11381255" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11381255</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.tzekov.2001.1319">Tzekov RT, Liu Y, Sohocki MM, Zack DJ, Daiger SP, Heckenlively JR, Birch DG. Autosomal dominant retinal degeneration and bone loss in patients with a 12-bp deletion in the CRX gene. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2001;<span class="ref-vol">42</span>:1319–27.</span> [<a href="/pmc/articles/PMC2581450/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2581450</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11328746" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11328746</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.van_der_spuy.2003.5396">van der Spuy J, Kim JH, Yu YS, Szel A, Luthert PJ, Clark BJ, Cheetham ME. The expression of the Leber congenital amaurosis protein AIPL1 coincides with rod and cone photoreceptor development. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2003;<span class="ref-vol">44</span>:5396–403.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14638743" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14638743</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.wang.2009.380">Wang H, den Hollander AI, Moayedi Y, Abulimiti A, Li Y, Collin RWJ, Hoyng CB, Lopez I, Bray M, Lewis RA, Lupski JR, Mardon G, Koenekoop RK, Chen R. Mutations in SPATA7 cause Leber congenital amaurosis and juvenile retinitis pigmentosa. <span><span class="ref-journal">Am J Hum Genet. </span>2009;<span class="ref-vol">84</span>:380–7.</span> [<a href="/pmc/articles/PMC2668010/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2668010</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19268277" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19268277</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.weleber.1998.580">Weleber RG. The dystrophic retina in multisystem disorders: the electroretinogram in neuronal ceroid lipofuscinoses. <span><span class="ref-journal">Eye. </span>1998;<span class="ref-vol">12</span>:580–90.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9775220" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9775220</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.weleber.2004.128">Weleber RG, Gupta N, Trzupek KM, Wepner MS, Kurz DE, Milam AH. Electroretinographic and clinicopathologic correlations of retinal dysfunction in infantile neuronal ceroid lipofuscinosis (infantile Batten disease). <span><span class="ref-journal">Mol Genet Metab. </span>2004;<span class="ref-vol">83</span>:128–37.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15464427" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15464427</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.weleber.2011.292">Weleber RG, Michaelides M, Trzupek KM, Stover NB, Stone EM. The phenotype of Severe Early Childhood Onset Retinal Dystrophy (SECORD) from mutation of RPE65 and differentiation from Leber congenital amaurosis. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2011;<span class="ref-vol">52</span>:292–302.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20811047" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20811047</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.zeitz.2006.657">Zeitz C, Kloeckener-Gruissem B, Forster U, Kohl S, Magyar I, Wissinger B, Matyas G, Borruat FX, Schorderet DF, Zrenner E, Munier FL, Berger W. Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause autosomal recessive night blindness. <span><span class="ref-journal">Am J Hum Genet. </span>2006;<span class="ref-vol">79</span>:657–67.</span> [<a href="/pmc/articles/PMC1592568/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1592568</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16960802" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16960802</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.zernant.2005.3052">Zernant J, Kulm M, Dharmaraj S, den Hollander AI, Perrault I, Preising MN, Lorenz B, Kaplan J, Cremers FP, Maumenee I, Koenekoop RK, Allikmets R. Genotyping microarray (disease chip) for Leber congenital amaurosis: detection of modifier alleles. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2005;<span class="ref-vol">46</span>:3052–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16123401" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16123401</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.zhao.2003.3965">Zhao Y, Hong DH, Pawlyk B, Yue G, Adamian M, Grynberg M, Godzik A, Li T. The retinitis pigmentosa GTPase regulator (RPGR)- interacting protein: subserving RPGR function and participating in disk morphogenesis. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2003;<span class="ref-vol">100</span>:3965–70.</span> [<a href="/pmc/articles/PMC153031/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC153031</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12651948" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12651948</span></a>]</div></p></li></ul></div><div id="lca.Suggested_Reading"><h3>Suggested Reading</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="lca.REF.koenekoop.2005.175">Koenekoop RK. RPGRIP1 is mutated in Leber congenital amaurosis: a mini-review. <span><span class="ref-journal">Ophthalmic Genet. </span>2005;<span class="ref-vol">26</span>:175–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16352478" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16352478</span></a>]</div></p></li></ul></div></div><div id="lca.Chapter_Notes"><h2 id="_lca_Chapter_Notes_">Chapter Notes</h2><div id="lca.Acknowledgments"><h3>Acknowledgments</h3><p>Supported in part by Foundation Fighting Blindness, Research to Prevent Blindness, and the Grousbeck Family Foundation.</p></div><div id="lca.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>24 May 2018 (ma) Retired chapter: covered in <a href="/books/n/gene/lca-ov/?report=reader">LCA/EOSRD Overview</a></div></li><li class="half_rhythm"><div>2 May 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>30 March 2010 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>12 October 2006 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>9 November 2005 (rw) Revision: <i>RDH12</i> gene identified</div></li><li class="half_rhythm"><div>7 July 2004 (me) Review posted live</div></li><li class="half_rhythm"><div>30 December 2003 (rw, pf, kt) Original submission</div></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1298_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Richard G Weleber</span>, MD, DABMG, FACMG<div class="affiliation small">Ophthalmic Genetics Clinic<br />Casey Eye Institute of Oregon Health Sciences University<br />Portland, Oregon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.usho@rrebelew" class="oemail">ude.usho@rrebelew</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Peter J Francis</span>, FRCOphth, PhD<div class="affiliation small">Pacific Ophthalmology Consulting, LLC<br />Portland, Oregon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.liamg@hthporetep" class="oemail">moc.liamg@hthporetep</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Karmen M Trzupek</span>, MS, CGC<div class="affiliation small">Hear See Hope Foundation<br />Seattle, Washington<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="moc.anddemrofni@kepuzrtk" class="oemail">moc.anddemrofni@kepuzrtk</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Catie Beattie</span>, MS, CGC<div class="affiliation small">Ophthalmic Genetics Clinic<br />Casey Eye Institute of Oregon Health Sciences University<br />Portland, Oregon<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ude.usho@eittaeb" class="oemail">ude.usho@eittaeb</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">July 7, 2004</span>; Last Update: <span itemprop="dateModified">May 2, 2013</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. 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contact: <a href="mailto:dev@null" data-email="ude.wu@tssamda" class="oemail">ude.wu@tssamda</a>.</p></div></div><h3>Publisher</h3><p><a href="http://www.washington.edu" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">University of Washington, Seattle</a>, Seattle (WA)</p><h3>NLM Citation</h3><p>Weleber RG, Francis PJ, Trzupek KM, et al. Leber Congenital Amaurosis – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2004 Jul 7 [Updated 2013 May 2]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gene/lathosterolosis/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gene/lca-ov/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figoblcaTmoleculargenetictestingusedin"><div id="lca.T.molecular_genetic_testing_used_in" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Leber Congenital Amaurosis</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene (Locus) <sup>1</sup></th><th id="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of LCA Attributed to Mutation of Gene</th><th id="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variants Detected <sup>2</sup></th></tr></thead><tbody><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>GUCY2D</i> (LCA1)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">6%-21%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>RPE65</i> (LCA2)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">3%-16%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>SPATA7</i> (LCA3)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>7</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in exons 5,6,11,12</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>AIPL1</i> (LCA4)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">4%-8%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>7</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in exons 2-6</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>LCA5</i> (LCA5)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">~1%-2%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>7</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in exons 3,4,5,7 <sup>4</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>RPGRIP1</i> (LCA6)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">~5%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>4</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in selected exons</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>CRX</i> (LCA7)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">~3%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>4</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>CRB1</i> (LCA8)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>4</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in selected exons</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>8</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>NMNAT1</i> (LCA9)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>CEP290</i> (LCA10)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">≤20%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>4</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in selected exons</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">41-variant panel <sup>4</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>IMPDH1</i> (LCA11)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Rare cause of dominant LCA</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>RD3</i> (LCA12)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>RDH12</i> (LCA13)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">~4%</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>LRAT</i> (LCA14)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>4</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in selected exons</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>TULP1</i> (LCA15)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup> of select exons <sup>4</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants in exons 9,10,12,13,14</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Targeted analysis for pathogenic variants</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See footnote 4.</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>KCNJ13</i><br />(LCA16)</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Partial- and whole-gene deletion/duplication <sup>6</sup></td></tr><tr><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>IQCB1</i>
|
|
</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown</td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_lca.T.molecular_genetic_testing_used_in_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence variants</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="lca.TF.1.1"><p class="no_margin">See <a href="/books/NBK1298/?report=reader#lca.molgen.TA">Table A. Genes and Databases</a> for protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="lca.TF.1.2"><p class="no_margin">See <a href="#lca.Molecular_Genetics">Molecular Genetics</a> for information on allelic variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="lca.TF.1.3"><p class="no_margin">Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click <a href="/books/n/gene/app2/?report=reader">here</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="lca.TF.1.4"><p class="no_margin">Pathogenic variants in panel may vary.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="lca.TF.1.5"><p class="no_margin">Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="lca.TF.1.6"><p class="no_margin">No deletions or duplications involving <i>GUCY2D</i>, <i>AIPL1</i>, <i>CEP290</i>, <i>IMPDH1</i>, <i>LRAT</i>, <i>NMNAT1</i>, <i>RD3</i>, <i>RDH12, RPGRIP1, RPE65, SPATA7, CRX,</i> or <i>KCNJ13</i> have been reported to cause LCA.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="lca.TF.1.7"><p class="no_margin">Exons sequenced may vary by laboratory.</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="lca.TF.1.8"><p class="no_margin">Whole-gene deletion reported [<a class="bibr" href="#lca.REF.stone.2007.791" rid="lca.REF.stone.2007.791">Stone 2007</a>]</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcamolgenTA"><div id="lca.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Leber Congenital Amaurosis: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Locus Name</th><th id="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA1</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/3000" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
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<i>GUCY2D</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=17&query=GUCY2D&qstr=GUCY2D&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">17p13<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q02846" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retinal guanylyl cyclase 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/gcmut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International (GUCY2D)</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=GUCY2D" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GUCY2D</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=GUCY2D[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GUCY2D</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA2</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="/gene/6121" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>RPE65</i>
|
|
</a>
|
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=1&query=RPE65&qstr=RPE65&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1p31<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q16518" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retinoid isomerohydrolase</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/rpe65mut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the RPE65 Gene</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=RPE65" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RPE65</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=RPE65[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RPE65</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA3</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="/gene/55812" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>SPATA7</i>
|
|
</a>
|
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=14&query=SPATA7&qstr=SPATA7&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">14q31<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q9P0W8" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Spermatogenesis-associated protein 7</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://grenada.lumc.nl/LOVD2/eye/home.php?select_db=SPATA7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SPATA7 @ LOVD</a>
|
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=SPATA7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SPATA7</a>
|
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=SPATA7[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">SPATA7</a>
|
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</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA4</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="/gene/23746" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>AIPL1</i>
|
|
</a>
|
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=17&query=AIPL1&qstr=AIPL1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">17p13<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q9NZN9" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Aryl-hydrocarbon-interacting protein-like 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/aipl1mut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Aryl Hydrocarbon Receptor-interacting Protein-like 1 (AIPL1)</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=AIPL1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AIPL1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=AIPL1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AIPL1</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA5</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/167691" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>LCA5</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=6&query=LCA5&qstr=LCA5&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">6q14<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q86VQ0" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lebercilin</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/LCA5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LCA5 database</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LCA5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LCA5</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=LCA5[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LCA5</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA6</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/57096" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>RPGRIP1</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=14&query=RPGRIP1&qstr=RPGRIP1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">14q11<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q96KN7" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">X-linked retinitis pigmentosa GTPase regulator-interacting protein 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/rpgripmu.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Retinitis Pigmentosa GTPase Regulator Interacting Protein Gene (RPGRIP)</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=RPGRIP1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RPGRIP1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=RPGRIP1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RPGRIP1</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA7</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/1406" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>CRX</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=19&query=CRX&qstr=CRX&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">19q13<wbr style="display:inline-block"></wbr>​.33</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O43186" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Cone-rod homeobox protein</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/crxmut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Cone Rod Homeobox Gene</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CRX" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CRX</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CRX[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CRX</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA8</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/23418" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>CRB1</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=1&query=CRB1&qstr=CRB1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1q31<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P82279" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Protein crumbs homolog 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/crb1mut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Human Crumbs Homologue 1 (CRB1)</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CRB1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CRB1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CRB1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CRB1</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA9</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/64802" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>NMNAT1</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=1&query=NMNAT1&qstr=NMNAT1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1p36<wbr style="display:inline-block"></wbr>​.22</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q9HAN9" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;"></td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=NMNAT1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NMNAT1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=NMNAT1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NMNAT1</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA10</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/80184" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>CEP290</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=12&query=CEP290&qstr=CEP290&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">12q21<wbr style="display:inline-block"></wbr>​.32</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O15078" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Centrosomal protein of 290 kDa</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;"></td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CEP290" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CEP290</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=CEP290[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CEP290</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA11</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/3614" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>IMPDH1</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=7&query=IMPDH1&qstr=IMPDH1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">7q32<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P20839" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Inosine-5'-monophosphate dehydrogenase 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/impdhmut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Inosine Monophosphate DehydrogenaseType 1 Gene (IMPDH1)</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=IMPDH1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IMPDH1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=IMPDH1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IMPDH1</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA12</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/343035" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>RD3</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=1&query=RD3&qstr=RD3&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">1q32<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q7Z3Z2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Protein RD3</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://grenada.lumc.nl/LOVD2/eye/home.php?select_db=RD3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RD3 @ LOVD</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=RD3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RD3</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=RD3[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RD3</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA13</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/145226" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>RDH12</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=14&query=RDH12&qstr=RDH12&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">14q24<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q96NR8" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retinol dehydrogenase 12</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://grenada.lumc.nl/LOVD2/eye/home.php?select_db=RDH12" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RDH12 @ LOVD</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=RDH12" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RDH12</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=RDH12[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">RDH12</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA14</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/9227" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>LRAT</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=4&query=LRAT&qstr=LRAT&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">4q32<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O95237" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Lecithin retinol acyltransferase</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/lratmut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Lecithin Retinol Acyltransferase Gene (LRAT)</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=LRAT" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LRAT</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=LRAT[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">LRAT</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA15</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/7287" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>TULP1</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=6&query=TULP1&qstr=TULP1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">6p21<wbr style="display:inline-block"></wbr>​.31</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O00294" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Tubby-related protein 1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.retina-international.org/files/sci-news/tulpmut.htm" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Retina International Mutations of the Tubby-like Protein 1 Gene</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=TULP1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TULP1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=TULP1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">TULP1</a>
|
|
</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">LCA16</td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/3769" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>KCNJ13</i>
|
|
</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=2&query=KCNJ13&qstr=KCNJ13&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2q37<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/O60928" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Inward rectifier potassium channel 13</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://grenada.lumc.nl/LOVD2/eye/home.php?select_db=KCNJ13" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">KCNJ13 @ LOVD</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=KCNJ13" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">KCNJ13</a>
|
|
</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=KCNJ13[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">KCNJ13</a>
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</td></tr><tr><td headers="hd_b_lca.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;"></td><td headers="hd_b_lca.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/9657" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>IQCB1</i>
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</a>
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/projects/mapview/maps.cgi?taxid=9606&chr=3&query=IQCB1&qstr=IQCB1&maps=snp,genes-r,pheno&zoom=2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">3q13<wbr style="display:inline-block"></wbr>​.33</a>
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
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<a href="http://www.uniprot.org/uniprot/Q15051" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IQ calmodulin-binding motif-containing protein 1</a>
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.LOVD.nl/IQCB1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IQCB1 @ LOVD</a>
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=IQCB1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IQCB1</a>
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</td><td headers="hd_b_lca.molgen.TA_1_1_1_7" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=IQCB1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">IQCB1</a>
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|
</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div id="lca.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
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<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
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chromosome locus from
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<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
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protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
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For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
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<a href="/books/n/gene/app1/?report=reader">here</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcamolgenTB"><div id="lca.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Leber Congenital Amaurosis (<a href="/omim/146690,180040,180069,204000,204100,600179,602225,603208,604210,604232,604392,604393,604537,604863,605446,608553,608700,608830,609237,609868,610142,610612,611408,611755,612712,613341,613826,613829,613835,613837,613843,614186" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">View All in OMIM</a>) </p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/146690" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">146690</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IMP DEHYDROGENASE 1; IMPDH1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/180040" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">180040</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RETINAL DEGENERATION 3, MOUSE, HOMOLOG OF; RD3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/180069" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">180069</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RETINAL PIGMENT EPITHELIUM-SPECIFIC PROTEIN, 65-KD; RPE65</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/204000" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">204000</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 1; LCA1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/204100" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">204100</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 2; LCA2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/600179" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600179</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">GUANYLATE CYCLASE 2D, MEMBRANE; GUCY2D</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/602225" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">602225</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CONE-ROD HOMEOBOX-CONTAINING GENE; CRX</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603208" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603208</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 13; KCNJ13</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604210" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604210</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CRUMBS, DROSOPHILA, HOMOLOG OF, 1; CRB1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604232" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604232</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 3; LCA3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604392" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604392</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ARYLHYDROCARBON-INTERACTING RECEPTOR PROTEIN-LIKE 1; AIPL1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604393" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604393</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 4; LCA4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604537" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604537</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 5; LCA5</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/604863" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">604863</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LECITHIN RETINOL ACYLTRANSFERASE; LRAT</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/605446" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">605446</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RETINITIS PIGMENTOSA GTPase REGULATOR-INTERACTING PROTEIN; RPGRIP1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/608553" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">608553</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 9; LCA9</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/608700" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">608700</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICOTINAMIDE NUCLEOTIDE ADENYLYLTRANSFERASE 1; NMNAT1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/608830" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">608830</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RETINOL DEHYDROGENASE 12; RDH12</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/609237" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">609237</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">IQ MOTIF-CONTAINING PROTEIN B1; IQCB1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/609868" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">609868</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SPERMATOGENESIS-ASSOCIATED PROTEIN 7; SPATA7</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/610142" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">610142</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CENTROSOMAL PROTEIN, 290-KD; CEP290</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/610612" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">610612</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 12; LCA12</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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|
<a href="/omim/611408" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611408</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LCA5 GENE; LCA5</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/611755" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611755</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 10; LCA10</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/612712" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">612712</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 13; LCA13</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/613341" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613341</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 14; LCA14</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/613826" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613826</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 6; LCA6</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<a href="/omim/613829" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613829</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 7; LCA7</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/613835" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613835</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 8; LCA8</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/613837" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613837</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 11; LCA11</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/613843" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613843</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 15; LCA15</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/614186" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">614186</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">LEBER CONGENITAL AMAUROSIS 16; LCA16</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figoblcaTgucy2dpathogenicvariantsdiscuss"><div id="lca.T.gucy2d_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p><i>GUCY2D</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.gucy2d_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.gucy2d_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.gucy2d_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_lca.T.gucy2d_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.gucy2d_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.gucy2d_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.3233-3236dup (4-bp insertion)</td><td headers="hd_h_lca.T.gucy2d_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.His1079GlnfsTer54</td><td headers="hd_h_lca.T.gucy2d_pathogenic_variants_discuss_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<a href="/nuccore/169791019" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000180<wbr style="display:inline-block"></wbr>​.3</a>
|
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<br />
|
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<a href="/protein/4504217" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000171<wbr style="display:inline-block"></wbr>​.1</a>
|
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTspata7pathogenicvariantsdiscuss"><div id="lca.T.spata7_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p><i>SPATA7</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.spata7_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.spata7_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change<br />(Alias <sup>1</sup>)</th><th id="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.322C>T</td><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg108Ter</td><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/154090977?report=genbank&log$=seqview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_018418<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="/protein/94536848?report=genpept&log$=seqview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_060888<wbr style="display:inline-block"></wbr>​.2</a>
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</td></tr><tr><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.960dupA<br />(961dupA)</td><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro321ThrfsTer6<br />(Pro321ThrfsTer326)</td></tr><tr><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1183C>T</td><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg395Ter</td></tr><tr><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1395delA<br />(1546delA)</td><td headers="hd_h_lca.T.spata7_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln465HisfsTer41<br />(Q465fsTer505)</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="lca.TF.3.1"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTaipl1pathogenicvariantsdiscusse"><div id="lca.T.aipl1_pathogenic_variants_discusse" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p><i>AIPL1</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.aipl1_pathogenic_variants_discusse/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.aipl1_pathogenic_variants_discusse_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.589G>C</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala197Pro</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_3" rowspan="7" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/74272275" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_014336<wbr style="display:inline-block"></wbr>​.3</a>
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<a href="/protein/74272276" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_055151<wbr style="display:inline-block"></wbr>​.3</a>
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</td></tr><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.617T>A</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ile206Asn</td></tr><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.715T>C</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Cys239Arg</td></tr><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.784G>A</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gly262Ser</td></tr><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.834G>A</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Trp278Ter</td></tr><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.905G>T</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg302Leu</td></tr><tr><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1126C>T</td><td headers="hd_h_lca.T.aipl1_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro376Ser</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTlca5pathogenicvariantsdiscussed"><div id="lca.T.lca5_pathogenic_variants_discussed" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p><i>LCA5</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.lca5_pathogenic_variants_discussed/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.lca5_pathogenic_variants_discussed_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.835C>T</td><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Gln279Ter</td><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_3" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/262359968" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_181714<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="/protein/170650670" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_859065<wbr style="display:inline-block"></wbr>​.2</a>
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</td></tr><tr><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1151delC</td><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro384GlnfsTer18</td></tr><tr><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1476dupA</td><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Pro493ThrfsTer2</td></tr><tr><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">g.(-19612)-(-18015)del1598</td><td headers="hd_h_lca.T.lca5_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTrpgrip1pathogenicvariantsdiscus"><div id="lca.T.rpgrip1_pathogenic_variants_discus" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p><i>RPGRIP1</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.rpgrip1_pathogenic_variants_discus/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.rpgrip1_pathogenic_variants_discus_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DNA Nucleotide Change</th><th id="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Predicted Protein Change</th><th id="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">c.1639G>T</td><td headers="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">p.Ala547Ser</td><td headers="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/nuccore/112734866" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_020366<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="/protein/112734867" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_065099<wbr style="display:inline-block"></wbr>​.3</a>
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</td></tr><tr><td headers="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">c.2480G>T</td><td headers="hd_h_lca.T.rpgrip1_pathogenic_variants_discus_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">p.Arg827Leu</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTcrxpathogenicvariantsdiscussed"><div id="lca.T.crx_pathogenic_variants_discussed" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p><i>CRX</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.crx_pathogenic_variants_discussed/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.crx_pathogenic_variants_discussed_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.crx_pathogenic_variants_discussed_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_lca.T.crx_pathogenic_variants_discussed_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.crx_pathogenic_variants_discussed_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.crx_pathogenic_variants_discussed_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.529delG</td><td headers="hd_h_lca.T.crx_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala177LeufsTer10</td><td headers="hd_h_lca.T.crx_pathogenic_variants_discussed_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/NM_000554.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000554<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="/protein/4557489" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000545<wbr style="display:inline-block"></wbr>​.1</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTcrb1pathogenicvariantsdiscussed"><div id="lca.T.crb1_pathogenic_variants_discussed" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p><i>CRB1</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.crb1_pathogenic_variants_discussed/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.crb1_pathogenic_variants_discussed_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.crb1_pathogenic_variants_discussed_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_lca.T.crb1_pathogenic_variants_discussed_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.crb1_pathogenic_variants_discussed_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.crb1_pathogenic_variants_discussed_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2843G>A</td><td headers="hd_h_lca.T.crb1_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Cys948Tyr</td><td headers="hd_h_lca.T.crb1_pathogenic_variants_discussed_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/41327707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_201253<wbr style="display:inline-block"></wbr>​.1</a>
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<a href="/protein/41327708" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_957705<wbr style="display:inline-block"></wbr>​.1</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTnmnat1pathogenicvariantsdiscuss"><div id="lca.T.nmnat1_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 9. </span></h3><div class="caption"><p><i>NMNAT1</i> Pathogenic Variants Discussed in This GeneReview</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.nmnat1_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.nmnat1_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.nmnat1_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Nucleotide Change</th><th id="hd_h_lca.T.nmnat1_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.nmnat1_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.nmnat1_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.769G>A</td><td headers="hd_h_lca.T.nmnat1_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu257Lys</td><td headers="hd_h_lca.T.nmnat1_pathogenic_variants_discuss_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/NM_022787.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_022787<wbr style="display:inline-block"></wbr>​.3</a>
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<a href="/protein/NP_073624.2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_073624<wbr style="display:inline-block"></wbr>​.2</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTcep290pathogenicvariantsdiscuss"><div id="lca.T.cep290_pathogenic_variants_discuss" class="table"><h3><span class="label">Table 10. </span></h3><div class="caption"><p><i>CEP290</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.cep290_pathogenic_variants_discuss/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.cep290_pathogenic_variants_discuss_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.cep290_pathogenic_variants_discuss_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DNA Nucleotide Change</th><th id="hd_h_lca.T.cep290_pathogenic_variants_discuss_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Predicted Protein Change</th><th id="hd_h_lca.T.cep290_pathogenic_variants_discuss_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.cep290_pathogenic_variants_discuss_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2991+1655A>G</td><td headers="hd_h_lca.T.cep290_pathogenic_variants_discuss_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Cys998Ter <sup>1</sup></td><td headers="hd_h_lca.T.cep290_pathogenic_variants_discuss_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/109255233" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_025114<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="/protein/109255234" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_079390<wbr style="display:inline-block"></wbr>​.3</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="lca.TF.10.1"><p class="no_margin">The aberrant splice product was reported in <a class="bibr" href="#lca.REF.den_hollander.2006.556" rid="lca.REF.den_hollander.2006.556">den Hollander et al [2006]</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTrd3pathogenicvariantsdiscussed"><div id="lca.T.rd3_pathogenic_variants_discussed" class="table"><h3><span class="label">Table 11. </span></h3><div class="caption"><p><i>RD3</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.rd3_pathogenic_variants_discussed/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.rd3_pathogenic_variants_discussed_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.rd3_pathogenic_variants_discussed_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_lca.T.rd3_pathogenic_variants_discussed_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted Protein Change</th><th id="hd_h_lca.T.rd3_pathogenic_variants_discussed_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.rd3_pathogenic_variants_discussed_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.296+1G>A</td><td headers="hd_h_lca.T.rd3_pathogenic_variants_discussed_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_lca.T.rd3_pathogenic_variants_discussed_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/212275922?report=genbank&log$=seqview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_183059<wbr style="display:inline-block"></wbr>​.2</a>
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<br />
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<a href="/protein/NP_898882.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_898882<wbr style="display:inline-block"></wbr>​.1</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figoblcaTrdh12pathogenicvariantsdiscusse"><div id="lca.T.rdh12_pathogenic_variants_discusse" class="table"><h3><span class="label">Table 12. </span></h3><div class="caption"><p><i>RDH12</i> Pathogenic Variants Discussed in This <i>GeneReview</i></p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1298/table/lca.T.rdh12_pathogenic_variants_discusse/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__lca.T.rdh12_pathogenic_variants_discusse_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_lca.T.rdh12_pathogenic_variants_discusse_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DNA Nucleotide Change</th><th id="hd_h_lca.T.rdh12_pathogenic_variants_discusse_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Predicted Protein Change</th><th id="hd_h_lca.T.rdh12_pathogenic_variants_discusse_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference Sequences</th></tr></thead><tbody><tr><td headers="hd_h_lca.T.rdh12_pathogenic_variants_discusse_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.806_810delCCCTG</td><td headers="hd_h_lca.T.rdh12_pathogenic_variants_discusse_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala269GlyfsTer2</td><td headers="hd_h_lca.T.rdh12_pathogenic_variants_discusse_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/nuccore/186928838" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_152443<wbr style="display:inline-block"></wbr>​.2</a>
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<br />
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<a href="/protein/186928839" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_689656<wbr style="display:inline-block"></wbr>​.2</a>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Variants listed in the table have been provided by the authors. <i>GeneReviews</i> staff have not independently verified the classification of variants.</p></div></dd></dl><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin"><i>GeneReviews</i> follows the standard naming conventions of the Human Genome Variation Society (<a href="https://varnomen.hgvs.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">varnomen<wbr style="display:inline-block"></wbr>​.hgvs.org</a>). See <a href="/books/n/gene/app3/?report=reader">Quick Reference</a> for an explanation of nomenclature.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script><script type="text/javascript">if (typeof (jQuery) != 'undefined') { (function ($) { $(function () { var min = Math.ceil(1); var max = Math.floor(100000); var randomNum = Math.floor(Math.random() * (max - min)) + min; var surveyUrl = "/projects/Gene/portal/surveys/seqdbui-survey.js?rando=" + randomNum.toString(); $.getScript(surveyUrl, function () { try { ncbi.seqDbUISurvey.init(); } catch (err) { console.info(err); } }).fail(function (jqxhr, settings, exception) { console.info('Cannot load survey script', jqxhr); });; }); })(jQuery); };</script></div></div>
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