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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Bestrophinopathies - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_inbook_title" content="GeneReviews® [Internet]">
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<meta name="citation_title" content="Bestrophinopathies">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2020/07/16">
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<meta name="citation_author" content="Ian M MacDonald">
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<meta name="citation_author" content="Thomas Lee">
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<meta name="citation_author" content="Jessica Lawrence">
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<meta name="citation_pmid" content="20301346">
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<meta name="citation_fulltext_html_url" content="https://www.ncbi.nlm.nih.gov/books/NBK1167/">
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<meta name="citation_keywords" content="Best Vitelliform Macular Dystrophy (BVMD)">
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<meta name="citation_keywords" content="BEST1 Adult-onset Vitelliform Macular Dystrophy (AVMD)">
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<meta name="citation_keywords" content="Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC)">
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<meta name="citation_keywords" content="Autosomal Recessive Bestrophinopathy (ARB)">
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<meta name="citation_keywords" content="Bestrophin-1">
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<meta name="citation_keywords" content="BEST1">
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<meta name="citation_keywords" content="Bestrophinopathies">
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<meta name="DC.Title" content="Bestrophinopathies">
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<meta name="DC.Publisher" content="University of Washington, Seattle">
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<meta name="DC.Contributor" content="Ian M MacDonald">
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<meta name="DC.Contributor" content="Thomas Lee">
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<meta name="DC.Contributor" content="Jessica Lawrence">
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<meta name="DC.Date" content="2020/07/16">
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<meta name="description" content="Bestrophinopathies, the spectrum of ophthalmic disorders caused by pathogenic variants in BEST1, are typically characterized by retinal degeneration. The four recognized phenotypes are the three autosomal dominant disorders: Best vitelliform macular dystrophy (BVMD), BEST1 adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC); and autosomal recessive bestrophinopathy (ARB). Onset is usually in the first decade (except AVMD in which onset is age 30 to 50 years). Slow visual deterioration is the usual course. Choroidal neovascularization can occur in rare cases. ADVIRC is also associated with panophthalmic involvement including nanophthalmos, microcornea, hyperopia, and narrow anterior chamber angle with angle closure glaucoma.">
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<meta name="og:title" content="Bestrophinopathies">
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<meta name="og:description" content="Bestrophinopathies, the spectrum of ophthalmic disorders caused by pathogenic variants in BEST1, are typically characterized by retinal degeneration. The four recognized phenotypes are the three autosomal dominant disorders: Best vitelliform macular dystrophy (BVMD), BEST1 adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC); and autosomal recessive bestrophinopathy (ARB). Onset is usually in the first decade (except AVMD in which onset is age 30 to 50 years). Slow visual deterioration is the usual course. Choroidal neovascularization can occur in rare cases. ADVIRC is also associated with panophthalmic involvement including nanophthalmos, microcornea, hyperopia, and narrow anterior chamber angle with angle closure glaucoma.">
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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"><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="_NBK1167_"><span class="title" itemprop="name">Bestrophinopathies</span></h1><p class="contribs">MacDonald IM, Lee T, Lawrence J.</p><p class="fm-aai"><a href="#_NBK1167_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 24 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="bvd.Summary" itemprop="description"><h2 id="_bvd_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Bestrophinopathies, the spectrum of ophthalmic disorders caused by pathogenic variants in <i>BEST1</i>, are typically characterized by retinal degeneration. The four recognized phenotypes are the three autosomal dominant disorders: Best vitelliform macular dystrophy (BVMD), <i>BEST1</i> adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC); and autosomal recessive bestrophinopathy (ARB). Onset is usually in the first decade (except AVMD in which onset is age 30 to 50 years). Slow visual deterioration is the usual course. Choroidal neovascularization can occur in rare cases. ADVIRC is also associated with panophthalmic involvement including nanophthalmos, microcornea, hyperopia, and narrow anterior chamber angle with angle closure glaucoma.</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of autosomal dominant bestrophinopathy is established in a proband with suggestive findings and a heterozygous <i>BEST1</i> pathogenic (or likely pathogenic) variant identified by molecular genetic testing. The diagnosis of autosomal recessive bestrophinopathy is established in a proband with suggestive findings and biallelic <i>BEST1</i> pathogenic variants.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> For individuals with significant visual impairment, referral to a low vision clinic; attention to special education needs for children with visual impairment; and occupational counseling. Regarding advanced BVMD fundus lesions, no clinical trials have compared conservative treatment vs laser photocoagulation for choroidal neovascularization (CNV) and hemorrhage. Also, there are no ongoing clinical trials regarding the effectiveness of treatment with anti-VEGF (vascular endothelial growth factor) agents.</p><p><i>Surveillance:</i> Annual ophthalmologic examination (including best corrected visual acuity, visual fields, and spectral domain optical coherence tomography) to monitor progression of fundus lesions and to evaluate for coincidental development of CNV; in childhood, perform annual ophthalmologic examinations to help prevent the development of amblyopia.</p><p><i>Agents/circumstances to avoid:</i> Cessation of smoking to help prevent neovascularization of the retina.</p><p><i>Evaluation of relatives at risk:</i> It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt ophthalmologic evaluation and routine follow up.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>BVMD, AVMD, and ADVIRC are inherited in an autosomal dominant (AD) manner. By definition, autosomal recessive bestrophinopathy (ARB) is inherited in an autosomal recessive (AR) manner.</p><ul><li class="half_rhythm"><div>AD bestrophinopathy. Each child of an affected individual has a 50% chance of inheriting the <i>BEST1</i> pathogenic variant.</div></li><li class="half_rhythm"><div>AR bestrophinopathy. If both parents are known to be heterozygous for a <i>BEST1</i> pathogenic variant, each sib of an affected individual has at conception 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></ul><p>Once the <i>BEST1</i> pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for a bestrophinopathy are possible.</p></div></div><div id="bvd.GeneReview_Scope"><h2 id="_bvd_GeneReview_Scope_"><i>GeneReview</i> Scope</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbvdTc"><a href="/books/NBK1167/table/bvd.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobbvdTc"><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="bvd.Tc"><a href="/books/NBK1167/table/bvd.Tc/?report=objectonly" target="object" rid-ob="figobbvdTc">Table</a></h4><p class="float-caption no_bottom_margin">Best vitelliform macular dystrophy (BVMD) Adult-onset vitelliform macular dystrophy (AVMD)</p></div></div></div><div id="bvd.Diagnosis"><h2 id="_bvd_Diagnosis_">Diagnosis</h2><p>No consensus diagnostic criteria for bestrophinopathies have been published.</p><div id="bvd.Suggestive_Findings"><h3>Suggestive Findings</h3><p>A bestrophinopathy <b>should be suspected</b> in individuals with following the ophthalmologic findings and electrophysiologic studies by phenotype, and family history.</p><p><b>Ophthalmologic</b>
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<b>findings by phenotype</b></p><ul><li class="half_rhythm"><div>Best vitelliform macular dystrophy (BVMD)</div><ul><li class="half_rhythm"><div>Onset age three to 15 years</div></li><li class="half_rhythm"><div>Fundus examination. A typical yellow yolk-like macular lesion may be present, usually bilateral, but in some cases unilateral. Multiple lesions and lesions outside the macula occur in at least 25% of individuals. See <a class="figpopup" href="/books/NBK1167/figure/bvd.F1/?report=objectonly" target="object" rid-figpopup="figbvdF1" rid-ob="figobbvdF1">Figure 1</a>, <a class="figpopup" href="/books/NBK1167/figure/bvd.F2/?report=objectonly" target="object" rid-figpopup="figbvdF2" rid-ob="figobbvdF2">Figure 2</a>, <a class="figpopup" href="/books/NBK1167/figure/bvd.F3/?report=objectonly" target="object" rid-figpopup="figbvdF3" rid-ob="figobbvdF3">Figure 3</a>.</div></li></ul></li><li class="half_rhythm"><div><i>BEST1</i> adult-onset vitelliform macular dystrophy (AVMD)</div><ul><li class="half_rhythm"><div>Onset age 30-50 years</div></li><li class="half_rhythm"><div>Fundus examination. Subretinal, small, circular, yellow vitelliform lesion; vitelliform lesion can become atrophic over time.</div></li></ul></li><li class="half_rhythm"><div>Autosomal dominant vitreoretinochoroidopathy (ADVIRC)</div><ul><li class="half_rhythm"><div>Onset in the first decade of life</div></li><li class="half_rhythm"><div>Fundus examination. Peripheral retinal pigmentation, white retinal opacities</div></li><li class="half_rhythm"><div>Other ocular findings. Nanophthalmos, hyperopia, microcornea, narrow-angle glaucoma</div></li></ul></li><li class="half_rhythm"><div>Autosomal recessive bestrophinopathy (ARB)</div><ul><li class="half_rhythm"><div>Onset in the first decade of life</div></li><li class="half_rhythm"><div>Fundus examination. White subretinal deposits with macular subretinal fluid</div></li></ul></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figbvdF1" co-legend-rid="figlgndbvdF1"><a href="/books/NBK1167/figure/bvd.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figbvdF1" rid-ob="figobbvdF1"><img class="small-thumb" src="/books/NBK1167/bin/bvd-Image001.gif" src-large="/books/NBK1167/bin/bvd-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndbvdF1"><h4 id="bvd.F1"><a href="/books/NBK1167/figure/bvd.F1/?report=objectonly" target="object" rid-ob="figobbvdF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Best vitelliform macular dystrophy: Vitelliform stage (Stage 2) </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figbvdF2" co-legend-rid="figlgndbvdF2"><a href="/books/NBK1167/figure/bvd.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figbvdF2" rid-ob="figobbvdF2"><img class="small-thumb" src="/books/NBK1167/bin/bvd-Image002.gif" src-large="/books/NBK1167/bin/bvd-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndbvdF2"><h4 id="bvd.F2"><a href="/books/NBK1167/figure/bvd.F2/?report=objectonly" target="object" rid-ob="figobbvdF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Best vitelliform macular dystrophy: Pseudohypopyon (Stage 3) </p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figbvdF3" co-legend-rid="figlgndbvdF3"><a href="/books/NBK1167/figure/bvd.F3/?report=objectonly" target="object" title="Figure 3. " class="img_link icnblk_img figpopup" rid-figpopup="figbvdF3" rid-ob="figobbvdF3"><img class="small-thumb" src="/books/NBK1167/bin/bvd-Image003.gif" src-large="/books/NBK1167/bin/bvd-Image003.jpg" alt="Figure 3. " /></a><div class="icnblk_cntnt" id="figlgndbvdF3"><h4 id="bvd.F3"><a href="/books/NBK1167/figure/bvd.F3/?report=objectonly" target="object" rid-ob="figobbvdF3">Figure 3. </a></h4><p class="float-caption no_bottom_margin">Best vitelliform macular dystrophy: Central scarring (Stage 4b) </p></div></div><p>
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<b>Electrophysiologic studies</b>
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</p><ul><li class="half_rhythm"><div><b>Electrooculogram (EOG)</b> measures indirectly the standing potential of the eye. A normal light peak / dark trough ratio (Arden ratio) is >1.8. (As the Arden ratio decreases with age after the fourth decade, this value is not absolute.)</div><ul><li class="half_rhythm"><div class="half_rhythm">BVMD. Usually abnormal with a reduced light peak / dark trough ratio (Arden ratio) <1.5, most often between 1.0 and 1.3.</div><div class="half_rhythm">Note: Occasionally individuals with molecularly confirmed Best vitelliform macular dystrophy have a normal EOG [<a class="bibr" href="#bvd.REF.testa.2008.1467" rid="bvd.REF.testa.2008.1467">Testa et al 2008</a>].</div></li><li class="half_rhythm"><div class="half_rhythm">AVMD. Normal or only slightly reduced</div></li><li class="half_rhythm"><div class="half_rhythm">ADVIRC. Abnormal</div></li><li class="half_rhythm"><div class="half_rhythm">ARB. Abnormal</div></li></ul></li><li class="half_rhythm"><div>
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<b>Full-field electroretinogram (ERG)</b>
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</div><ul><li class="half_rhythm"><div>BVMD and AVMD. Normal</div></li><li class="half_rhythm"><div>ADVIRC. Normal or reduced</div></li><li class="half_rhythm"><div>ARB. Reduced scotopic and photopic responses</div></li></ul></li><li class="half_rhythm"><div>
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<b>Spectral-domain optical coherence tomography (OCT)</b>
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</div><ul><li class="half_rhythm"><div>BVMD and AVMD. Splitting and elevation of outer retina and retinal pigment epithelial layer with dome-like hyporeflective or hyperreflective material and subretinal fluid</div></li><li class="half_rhythm"><div>ADVIRC. Retinal atrophy usually present; possible cystoid macular edema</div></li><li class="half_rhythm"><div>ARB. Subretinal deposits with subretinal and/or intraretinal fluid</div></li></ul></li><li class="half_rhythm"><div>
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<b>Fundus autofluorescence (AF)</b>
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</div><ul><li class="half_rhythm"><div>BVMD and AVMD. Hyperautofluorescence at early stages progressing to hypofluorescence in late atrophic stages</div></li><li class="half_rhythm"><div>ADVIRC. Typically normal centrally with blocked fluorescence in the periphery</div></li><li class="half_rhythm"><div>ARB. Diffuse, discrete small areas of hyper- and hypoautofluorescence</div></li></ul></li></ul><p><b>Family history</b> is typically consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations); however, autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity) has been reported in some families. Absence of a known family history does not preclude the diagnosis.</p></div><div id="bvd.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of bestrophinopathy <b>is established</b> in a proband with <a href="#bvd.Suggestive_Findings">suggestive findings</a> and a heterozygous <i>BEST1</i> pathogenic (or likely pathogenic) variant or biallelic <i>BEST1</i> pathogenic (or likely pathogenic) variants identified by molecular genetic testing (see <a href="/books/NBK1167/table/bvd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobbvdTmoleculargenetictestingusedin">Table 1</a>).</p><p>Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variants" and "likely pathogenic variants" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [<a class="bibr" href="#bvd.REF.richards.2015.405" rid="bvd.REF.richards.2015.405">Richards et al 2015</a>]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a variant(s) of uncertain significance does not establish or rule out the diagnosis of bestrophinopathy.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (single-gene testing, multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing and genome sequencing) depending on the phenotype.</p><p>Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in <a href="#bvd.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#bvd.Option_1">Option 1</a>), whereas those in whom the diagnosis of a bestrophinopathy has not been considered may be more likely to be diagnosed using genomic testing (see <a href="#bvd.Option_2">Option 2</a>).</p><div id="bvd.Option_1"><h4>Option 1</h4><p><b>Single-gene testing.</b> Sequence analysis of <i>BEST1</i> is performed first to detect small intragenic deletions/insertions and missense, nonsense, and splice site variants. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.</p><p><b>Targeted analysis</b> for the c.383G>C pathogenic variant can be performed first in individuals of Swedish ancestry ("pedigree S1" in <a class="bibr" href="#bvd.REF.petrukhin.1998.241" rid="bvd.REF.petrukhin.1998.241">Petrukhin et al [1998]</a>). See <a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobbvdTnotablebest1pathogenicvariants">Table 3</a>).</p><p><b>A multigene panel</b> that includes <i>BEST1</i> and other genes of interest (see <a href="#bvd.Differential_Diagnosis">Differential Diagnosis</a>) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this <i>GeneReview</i>. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.</p><p>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>.</p></div><div id="bvd.Option_2"><h4>Option 2</h4><p><b>Comprehensive genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is the most commonly used genomic testing method; <b>genome sequencing</b> is also possible.</p><p>For an introduction to comprehensive genomic testing click <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing">here</a>. More detailed information for clinicians ordering genomic testing can be found <a href="/books/n/gene/app5/?report=reader#app5.Comprehensive_Genomic_Testing_1">here</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbvdTmoleculargenetictestingusedin"><a href="/books/NBK1167/table/bvd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobbvdTmoleculargenetictestingusedin"><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="bvd.T.molecular_genetic_testing_used_in"><a href="/books/NBK1167/table/bvd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object" rid-ob="figobbvdTmoleculargenetictestingusedin">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Bestrophinopathies </p></div></div></div></div></div><div id="bvd.Clinical_Characteristics"><h2 id="_bvd_Clinical_Characteristics_">Clinical Characteristics</h2><div id="bvd.Clinical_Description"><h3>Clinical Description</h3><p>Bestrophinopathies, the spectrum of ophthalmic disorders caused by pathogenic variants in <i>BEST1</i>, are typically characterized by retinal degeneration but may also be pan ophthalmic. The four recognized phenotypes are the three autosomal dominant disorders: Best vitelliform macular dystrophy (BVMD), <i>BEST1</i> adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC); and autosomal recessive bestrophinopathy (ARB).</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbvdTbestrophinopathiesfrequencyofph"><a href="/books/NBK1167/table/bvd.T.bestrophinopathies_frequency_of_ph/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobbvdTbestrophinopathiesfrequencyofph"><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="bvd.T.bestrophinopathies_frequency_of_ph"><a href="/books/NBK1167/table/bvd.T.bestrophinopathies_frequency_of_ph/?report=objectonly" target="object" rid-ob="figobbvdTbestrophinopathiesfrequencyofph">Table 2. </a></h4><p class="float-caption no_bottom_margin">Bestrophinopathies: Frequency of Phenotypes </p></div></div><div id="bvd.Best_Vitelliform_Macular_Dystrophy_B"><h4>Best Vitelliform Macular Dystrophy (BVMD)</h4><p>BVMD is a slowly progressive macular dystrophy typically with juvenile onset. The characteristic "egg yolk"-like lesion can be either unilateral or bilateral, single or multiple, and macular or eccentric. Retinal lesions progress from the "egg yolk" or vitelliform stage to a vitelliruptive form and finally to an end-stage form with macular scarring or neovascularization [<a class="bibr" href="#bvd.REF.macdonald.2012.123" rid="bvd.REF.macdonald.2012.123">MacDonald et al 2012</a>, <a class="bibr" href="#bvd.REF.boon.2013.809" rid="bvd.REF.boon.2013.809">Boon et al 2013</a>]. Inter- as well as intrafamilial variability is observed.</p><p>Although the following clinical stages have been described, it is important to note that the disease does not progress through each of these stages in every individual:</p><ul><li class="half_rhythm"><div><b>Stage 0.</b> Normal macula. Abnormal electrooculogram (EOG)</div></li><li class="half_rhythm"><div><b>Stage 1.</b> Retinal pigment epithelium (RPE) disruption in the macular region. Fluorescein angiogram (FA) shows window defects.</div></li><li class="half_rhythm"><div><b>Stage 2.</b> Circular well-circumscribed yellow-opaque homogeneous yolk-like macular lesion (vitelliform lesion) (see <a class="figpopup" href="/books/NBK1167/figure/bvd.F1/?report=objectonly" target="object" rid-figpopup="figbvdF1" rid-ob="figobbvdF1">Figure 1</a>). FA reveals marked hypofluorescence in the zone covered by the lesion.</div></li><li class="half_rhythm"><div><b>Stage 2a.</b> Vitelliform lesion contents become less homogeneous to develop a "scrambled-egg" appearance. FA shows partial blockage of fluorescence with a non-homogeneous hyperfluorescence.</div></li><li class="half_rhythm"><div><b>Stage 3.</b> Pseudohypopyon phase (see <a class="figpopup" href="/books/NBK1167/figure/bvd.F2/?report=objectonly" target="object" rid-figpopup="figbvdF2" rid-ob="figobbvdF2">Figure 2</a>). The lesion develops a fluid level of a yellow-colored vitelline substance. FA shows inferior hypofluorescence from the blockage by the vitelline material, along with superior hyperfluorescent defects.</div></li><li class="half_rhythm"><div><b>Stage 4a.</b> Orange-red lesion with atrophic RPE and visibility of the choroid. FA shows hyperfluorescence without leakage.</div></li><li class="half_rhythm"><div><b>Stage 4b.</b> Fibrous scarring of the macula (see <a class="figpopup" href="/books/NBK1167/figure/bvd.F3/?report=objectonly" target="object" rid-figpopup="figbvdF3" rid-ob="figobbvdF3">Figure 3</a>). FA shows hyperfluorescence without leakage.</div></li><li class="half_rhythm"><div><b>Stage 4c.</b> Choroidal neovascularization with new vessels on the fibrous scar or appearance of subretinal hemorrhage. FA shows hyperfluorescence as a result of neovascularization and leakage.</div></li></ul><p>
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<b>Other findings</b>
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</p><ul><li class="half_rhythm"><div><b>Electroretinogram (ERG).</b> While the full-field ERG is normal, foveal ERG or multifocal ERG reveals reduced central amplitudes [<a class="bibr" href="#bvd.REF.scholl.2002.1053" rid="bvd.REF.scholl.2002.1053">Scholl et al 2002</a>, <a class="bibr" href="#bvd.REF.palmowski.2003.145" rid="bvd.REF.palmowski.2003.145">Palmowski et al 2003</a>]. Abnormal multifocal ERG (mfERG) recordings match areas defined as clinically abnormal by optical coherence tomography (OCT) and retinal photography [<a class="bibr" href="#bvd.REF.glybina.2006.1593" rid="bvd.REF.glybina.2006.1593">Glybina & Frank 2006</a>]. Scanning laser ophthalmoscope-evoked multifocal ERG, used for topographic mapping of retinal function in individuals with BVMD, reveals significantly reduced amplitudes in the macula [<a class="bibr" href="#bvd.REF.rudolph.2003.154" rid="bvd.REF.rudolph.2003.154">Rudolph & Kalpadakis 2003</a>].</div></li><li class="half_rhythm"><div><b>Color vision tests.</b> While a significant proportion of individuals with BVMD have anomalous color discrimination particularly in the protan axis, color vision changes are nonspecific and not diagnostic.</div></li><li class="half_rhythm"><div><b>OCT</b> can reveal the cross-sectional anatomy of the retina in BVMD [<a class="bibr" href="#bvd.REF.pianta.2003.203" rid="bvd.REF.pianta.2003.203">Pianta et al 2003</a>, <a class="bibr" href="#bvd.REF.querques.2008.501" rid="bvd.REF.querques.2008.501">Querques et al 2008</a>]. OCT has defined normal retinal architecture or subtle changes in the outer retina in previtelliform clinical stages, splitting and elevation at the outer retina – retinal pigment epithelium complex in intermediate clinical stages, and thinning of the retina and retinal pigment epithelium in the atrophic clinical stage.</div></li><li class="half_rhythm"><div><b>Pathology.</b> See <a class="figpopup" href="/books/NBK1167/figure/bvd.F4/?report=objectonly" target="object" rid-figpopup="figbvdF4" rid-ob="figobbvdF4">Figure 4</a> and <a class="figpopup" href="/books/NBK1167/figure/bvd.F5/?report=objectonly" target="object" rid-figpopup="figbvdF5" rid-ob="figobbvdF5">Figure 5</a>.</div></li></ul><div class="iconblock whole_rhythm clearfix ten_col fig" id="figbvdF4" co-legend-rid="figlgndbvdF4"><a href="/books/NBK1167/figure/bvd.F4/?report=objectonly" target="object" title="Figure 4. " class="img_link icnblk_img figpopup" rid-figpopup="figbvdF4" rid-ob="figobbvdF4"><img class="small-thumb" src="/books/NBK1167/bin/bvd-Image004.gif" src-large="/books/NBK1167/bin/bvd-Image004.jpg" alt="Figure 4. " /></a><div class="icnblk_cntnt" id="figlgndbvdF4"><h4 id="bvd.F4"><a href="/books/NBK1167/figure/bvd.F4/?report=objectonly" target="object" rid-ob="figobbvdF4">Figure 4. </a></h4><p class="float-caption no_bottom_margin">Right eye of a male age 72 years with molecularly confirmed Best disease A. Macula shows loss of photoreceptor cells and an attenuated outer plexiform layer (OPL).</p></div></div><div class="iconblock whole_rhythm clearfix ten_col fig" id="figbvdF5" co-legend-rid="figlgndbvdF5"><a href="/books/NBK1167/figure/bvd.F5/?report=objectonly" target="object" title="Figure 5. " class="img_link icnblk_img figpopup" rid-figpopup="figbvdF5" rid-ob="figobbvdF5"><img class="small-thumb" src="/books/NBK1167/bin/bvd-Image005.gif" src-large="/books/NBK1167/bin/bvd-Image005.jpg" alt="Figure 5. " /></a><div class="icnblk_cntnt" id="figlgndbvdF5"><h4 id="bvd.F5"><a href="/books/NBK1167/figure/bvd.F5/?report=objectonly" target="object" rid-ob="figobbvdF5">Figure 5. </a></h4><p class="float-caption no_bottom_margin">Left eye of the same individual A. Macula shows loss of photoreceptor cells and attenuated OPL.</p></div></div></div><div id="bvd.BEST1_AdultOnset_Vitelliform_Macular"><h4><i>BEST1</i> Adult-Onset Vitelliform Macular Dystrophy (AVMD)</h4><p>AVMD is part of a group of conditions called pattern dystrophy (see <a href="#bvd.Differential_Diagnosis">Differential Diagnosis</a>).</p><p>Affected individuals usually become symptomatic in the fifth decade with typical onset between ages 30 and 50 years. Some individuals may be asymptomatic or have reduced visual acuity and metamorphopsia. Slow visual deterioration is the usual course. Choroidal neovascularization can occur in rare cases.</p><p>The yellow subfoveal deposits are about one third disc diameter size and will diminish over time to become atrophic. The vitelliform lesion is subretinal with heterogeneous hyperreflectivity and half of eyes can have pigment epithelial detachments.</p></div><div id="bvd.Autosomal_Dominant_Vitreoretinochoro"><h4>Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC)</h4><p>ADVIRC is characterized by circumscribed hyperpigmentation in the peripheral retina. A sharp demarcation line exists in the midperiphery between normal and abnormal retina. White pre-retinal opacities occur with the areas of hyperpigmentation. Cystoid macular degeneration is common along with pre-retinal neovascularization. Vitreous cells and vitreous fibrillar condensation can obscure vision. Affected individuals maintain good visual acuity until later in the disease course, when the entire retina becomes involved.</p><p>There is an association with nanophthalmos, microcornea, hyperopia, and narrow anterior chamber angle with angle closure glaucoma [<a class="bibr" href="#bvd.REF.yardley.2004.3683" rid="bvd.REF.yardley.2004.3683">Yardley et al 2004</a>].</p></div><div id="bvd.Autosomal_Recessive_Bestrophinopathy"><h4>Autosomal Recessive Bestrophinopathy (ARB)</h4><p>Typical age of onset in ARB is in the first decade but can be as late as the fifth decade. ARB is a more severe retinopathy than BVMD. Visual acuity can range from normal to less than 20/200 depending on the macular involvement of the disease.</p><p>The multifocal subretinal yellow deposits seen in the macula and peripheral retina are associated with subretinal fibrosis and intraretinal and subretinal fluid.</p><p>Affected individuals are hyperopic with shallow anterior chambers, making them prone to angle closure glaucoma.</p><p>Six children from three different families had biallelic pathogenic variants in <i>BEST1</i> [<a class="bibr" href="#bvd.REF.bitner.2011.5332" rid="bvd.REF.bitner.2011.5332">Bitner et al 2011</a>, <a class="bibr" href="#bvd.REF.iannaccone.2011.211" rid="bvd.REF.iannaccone.2011.211">Iannaccone et al 2011</a>, <a class="bibr" href="#bvd.REF.zhao.2012.866" rid="bvd.REF.zhao.2012.866">Zhao et al 2012</a>] (see <a href="#bvd.GenotypePhenotype_Correlations">Genotype-Phenotype Correlations</a>). Four of the six had multiple vitelliform lesions. Heterozygotes (i.e., carriers) did not develop disease.</p></div></div><div id="bvd.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>For most <i>BEST1</i> variants, genotype-phenotype correlations have not been demonstrated. However, a few missense variants have been associated with a milder phenotype:</p><ul><li class="half_rhythm"><div>A family with a <a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobbvdTnotablebest1pathogenicvariants">p.Val89Ala</a> substitution had late-onset visual failure (age 40-50 years) [<a class="bibr" href="#bvd.REF.eksandh.2001.107" rid="bvd.REF.eksandh.2001.107">Eksandh et al 2001</a>].</div></li><li class="half_rhythm"><div>A family with <a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobbvdTnotablebest1pathogenicvariants">p.Tyr227Asn</a> had late-onset small vitelliform lesions [<a class="bibr" href="#bvd.REF.mullins.2005.1588" rid="bvd.REF.mullins.2005.1588">Mullins et al 2005</a>].</div></li><li class="half_rhythm"><div><a class="bibr" href="#bvd.REF.khan.2018.606" rid="bvd.REF.khan.2018.606">Khan et al [2018]</a> described affected individuals and families with the <a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobbvdTnotablebest1pathogenicvariants">p.Ala243Val</a> variant and late-onset disease with a distinct pattern of fundus autofluorescence. This variant was previously associated with mild disease [<a class="bibr" href="#bvd.REF.boon.2009.187" rid="bvd.REF.boon.2009.187">Boon et al 2009</a>, <a class="bibr" href="#bvd.REF.querques.2011.4678" rid="bvd.REF.querques.2011.4678">Querques et al 2011</a>].</div></li></ul><p>Other observations:</p><ul><li class="half_rhythm"><div>Six children from three different families had biallelic pathogenic variants in <i>BEST1</i> [<a class="bibr" href="#bvd.REF.bitner.2011.5332" rid="bvd.REF.bitner.2011.5332">Bitner et al 2011</a>, <a class="bibr" href="#bvd.REF.iannaccone.2011.211" rid="bvd.REF.iannaccone.2011.211">Iannaccone et al 2011</a>, <a class="bibr" href="#bvd.REF.zhao.2012.866" rid="bvd.REF.zhao.2012.866">Zhao et al 2012</a>]. Three of the six were compound heterozygotes for the variants p.Leu41Pro and p.Ile201Thr; two of the six were homozygous for the c.1415delT variant; and one of the six was a compound heterozygote for p.Arg141Ser and p.Arg141His. Heterozygotes (i.e., carriers) did not develop disease.</div></li><li class="half_rhythm"><div><i>BEST1</i> variants that affect splicing cause ADVIRC [<a class="bibr" href="#bvd.REF.yardley.2004.3683" rid="bvd.REF.yardley.2004.3683">Yardley et al 2004</a>].</div></li></ul></div><div id="bvd.Penetrance"><h3>Penetrance</h3><p>BVMD shows high but reduced (>70%) penetrance, especially when electrooculogram is used as evidence of clinical expression.</p><p>Individuals heterozygous for a <i>BEST1</i> variant associated with ARB are generally clinically unaffected [<a class="bibr" href="#bvd.REF.zhao.2012.866" rid="bvd.REF.zhao.2012.866">Zhao et al 2012</a>].</p><p>Nomenclature</p><p>Other terms used to refer to BVMD include Best disease, early-onset vitelliform macular dystrophy, juvenile-onset vitelliform macular dystrophy, and polymorphic vitelline macular degeneration.</p></div><div id="bvd.Prevalence"><h3>Prevalence</h3><p>BVMD is a rare disorder. The prevalence has been estimated at 1:5,500 in a North American population [<a class="bibr" href="#bvd.REF.dalvin.2017.143" rid="bvd.REF.dalvin.2017.143">Dalvin et al 2017</a>].</p><p>The <i>BEST1</i> founder variant <a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobbvdTnotablebest1pathogenicvariants">c.383G>C</a> (p.Trp93Cys) has been identified in individuals who can trace their ancestry to a large Swedish kindred ("pedigree S1" in <a class="bibr" href="#bvd.REF.petrukhin.1998.241" rid="bvd.REF.petrukhin.1998.241">Petrukhin et al [1998]</a>).</p></div></div><div id="bvd.Genetically_Related_Allelic_Disorder"><h2 id="_bvd_Genetically_Related_Allelic_Disorder_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are confirmed to be associated with germline pathogenic variants in <i>BEST1</i>.</p><p>Note: Although <i>BEST1</i> variants have been identified in some individuals with a retinitis pigmentosa (RP)-like retinal dystrophy [<a class="bibr" href="#bvd.REF.davidson.2009.581" rid="bvd.REF.davidson.2009.581">Davidson et al 2009</a>], the diagnosis of RP in these individuals has been disputed. <a class="bibr" href="#bvd.REF.johnson.2017.45" rid="bvd.REF.johnson.2017.45">Johnson et al [2017]</a> have suggested that <i>BEST1</i>-related RP-like retinal dystrophy may be multigenic in etiology. It is also possible that the observed RP-like phenotype was caused by a separate, unidentified genetic variant in these individuals and that the identification of a <i>BEST1</i> variant was an incidental finding or a modifying factor. Further research is warranted.</p></div><div id="bvd.Differential_Diagnosis"><h2 id="_bvd_Differential_Diagnosis_">Differential Diagnosis</h2><p>Best vitelliform macular dystrophy (BVMD) is the second most common hereditary macular dystrophy. The most common heritable juvenile-onset macular dystrophy is Stargardt disease.</p><p>Although the cause of adult-onset vitelliform macular dystrophy (AVMD) in most individuals is unknown, this phenotype is observed in the spectrum of bestrophinopathies and with heterozygous pathogenic variants in <i>PRPH2</i> (encoding peripherin-2) (OMIM <a href="https://omim.org/entry/179605" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">179605</a>), <i>IMPG1</i> (OMIM <a href="https://omim.org/entry/616151" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616151</a>) and <i>IMPG2</i> (OMIM <a href="https://omim.org/entry/616152" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">616152</a>).</p><p><b>Choroidal neovascularization</b> is an acquired disorder.</p></div><div id="bvd.Management"><h2 id="_bvd_Management_">Management</h2><p>No clinical practice guidelines for bestrophinopathies have been published.</p><div id="bvd.Evaluations_Following_Initial_Diagno"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with a bestrophinopathy, the evaluations summarized below (if not performed as part of the evaluation that led to the diagnosis) are recommended:</p><ul><li class="half_rhythm"><div>Ophthalmologic examination, including best-corrected visual acuity, fundus examination, fundus photographs, and spectral-domain optical coherence tomography (SD-OCT) to determine the stage of disease</div></li><li class="half_rhythm"><div>Consultation with a low vision specialist/clinic as needed</div></li><li class="half_rhythm"><div>Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of bestrophinopathies in order to facilitate medical and personal decision making</div></li></ul></div><div id="bvd.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><p>Low vision aids benefit those individuals with significantly reduced visual acuity.</p><p>In the United States (US), educational issues for children with visual impairment can be addressed in the following:</p><ul><li class="half_rhythm"><div>Individualized education plan (IEP) services:</div><ul><li class="half_rhythm"><div>An IEP provides specially designed instruction and related services to children who qualify.</div></li><li class="half_rhythm"><div>IEP services will be reviewed annually to determine whether any changes are needed.</div></li><li class="half_rhythm"><div>As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate.</div></li><li class="half_rhythm"><div>Vision consultants should be a part of the child's IEP team to support access to academic material.</div></li></ul></li><li class="half_rhythm"><div>A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.</div></li></ul><p>Occupational counseling, often available through state agencies, patient advocacy groups, and health plans, should be offered.</p><p>Best vitelliform macular dystrophy (BVMD) stage 4c fundus lesions (see <a href="#bvd.Clinical_Description">Clinical Description</a>) or choroidal neovascularization and hemorrhage can be managed by direct laser photocoagulation. <a class="bibr" href="#bvd.REF.marano.2000.760" rid="bvd.REF.marano.2000.760">Marano et al [2000]</a> suggested a conservative approach in the treatment of choroidal neovascularization based on two individuals with BVMD whose visual acuity improved. No clinical trials comparing the efficacy of laser photocoagulation to conservative treatment have been conducted.</p><p>Anti-VEGF (vascular endothelial growth factor) agents are the standard treatment for individuals with subfoveal choroidal neovascularization (CNV). <a class="bibr" href="#bvd.REF.leu.2007.1723" rid="bvd.REF.leu.2007.1723">Leu et al [2007]</a> injected intravitreal bevacizumab in a boy age 13 years with BVMD and CNV, hastening visual recovery and regression of the CNV. Intravitreal ranibizumab has also been used with success [<a class="bibr" href="#bvd.REF.querques.2009.2960" rid="bvd.REF.querques.2009.2960">Querques et al 2009</a>]. There are no reports on the use of aflibercept. Long-term follow up of these affected individuals is unknown. Currently there are no clinical trials to demonstrate the effectiveness of anti-VEGF agents on CNV in BVMD.</p><p><a class="bibr" href="#bvd.REF.andrade.2003.1179" rid="bvd.REF.andrade.2003.1179">Andrade et al [2003]</a> performed photodynamic therapy (PDT) using verteporfin for CNV on one person with BVMD. The CNV regressed and the subretinal hemorrhage resolved. The authors suggested that PDT may be an option for treatment of CNV in BVMD.</p></div><div id="bvd.Surveillance"><h3>Surveillance</h3><p>Ophthalmologic examination (including best-corrected visual acuity, visual fields, and SD-OCT) should be performed annually to monitor the progression of the fundus lesions and to evaluate for coincident development of choroidal neovascularization (CNV).</p><p>In children, annual examinations are important in preventing the development of amblyopia, especially if there is a significant difference in the best-corrected visual acuity of one eye. A trial of conventional patching therapy of the better-seeing eye may be able to determine if amblyopia is present.</p><p>Affected individuals should be advised to see their ophthalmologist in the event of decreased vision or metamorphopsia (straight lines appearing wavy), which could be signs of CNV. In some cases, affected individuals can be advised to use an Amsler grid for self-evaluation.</p></div><div id="bvd.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>Cessation of smoking helps prevent neovascularization of the retina [<a class="bibr" href="#bvd.REF.clemons.2005.533" rid="bvd.REF.clemons.2005.533">Clemons et al 2005</a>].</p></div><div id="bvd.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from prompt ophthalmologic evaluation and routine follow up.</p><p>See <a href="#bvd.Related_Genetic_Counseling_Issues"><u>Genetic Counseling</u></a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="bvd.Therapies_Under_Investigation"><h3>Therapies Under Investigation</h3><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. Note: There may not be clinical trials for this disorder.</p></div></div><div id="bvd.Genetic_Counseling"><h2 id="_bvd_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="bvd.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Best vitelliform macular dystrophy (BVMD), <i>BEST1</i> adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC) are inherited in an autosomal dominant manner.</p><p>By definition, autosomal recessive bestrophinopathy (ARB) is inherited in an autosomal recessive manner.</p></div><div id="bvd.Autosomal_Dominant_Inheritance__Risk"><h3>Autosomal Dominant Inheritance – 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 individuals diagnosed with BVMD, AVMD, or ADVIRC have an affected parent.</div></li><li class="half_rhythm"><div>A proband with BVMD, AVMD, or ADVIRC may have the disorder as the result of a <i>de novo</i> pathogenic variant [<a class="bibr" href="#bvd.REF.apushkin.2006.887" rid="bvd.REF.apushkin.2006.887">Apushkin et al 2006</a>, <a class="bibr" href="#bvd.REF.li.2006.408" rid="bvd.REF.li.2006.408">Li et al 2006</a>, <a class="bibr" href="#bvd.REF.marchant.2007.e70" rid="bvd.REF.marchant.2007.e70">Marchant et al 2007</a>, <a class="bibr" href="#bvd.REF.atchaneeyasakul.2008.139" rid="bvd.REF.atchaneeyasakul.2008.139">Atchaneeyasakul et al 2008</a>, <a class="bibr" href="#bvd.REF.testa.2008.1467" rid="bvd.REF.testa.2008.1467">Testa et al 2008</a>]. The proportion of individuals with bestrophinopathy caused by a <i>de novo</i> pathogenic variant is unknown.</div></li><li class="half_rhythm"><div>Molecular genetic testing is recommended for the parents of a proband to confirm their genetic status and to allow reliable recurrence risk counseling. Note: Fundoscopic examination may be unreliable for the evaluation of the parents because the fundus may appear normal in affected individuals.</div></li><li class="half_rhythm"><div>If the pathogenic variant identified in the proband is not identified in either parent, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>The proband has a <i>de novo</i> pathogenic variant. Note: A pathogenic variant is reported as "<i>de novo</i>" if: (1) the pathogenic variant found in the proband is not detected in parental DNA; and (2) parental identity testing has confirmed biological maternity and paternity. If parental identity testing is not performed, the variant is reported as "assumed <i>de novo</i>" [<a class="bibr" href="#bvd.REF.richards.2015.405" rid="bvd.REF.richards.2015.405">Richards et al 2015</a>].</div></li><li class="half_rhythm"><div>The proband inherited a pathogenic variant from a parent with germline (or somatic and germline) mosaicism. Though theoretically possible, no instances of a proband inheriting a pathogenic variant from a parent with germline mosaicism have been reported. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism.</div></li></ul></li><li class="half_rhythm"><div>The family history of some individuals diagnosed with BVMD, AVMD, or ADVIRC may appear to be negative because of failure to recognize the disorder in family members and/or reduced penetrance in a heterozygous parent. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the pathogenic variant identified in the proband.</div></li></ul><p><b>Sibs of a proband.</b> The risk to the sibs depends on the genetic status of the proband's parents:</p><ul><li class="half_rhythm"><div>If a parent of the proband is affected and/or is known to have the pathogenic variant identified in the proband, the risk to the sibs is 50%. Note: The age of onset, clinical manifestations, and degree of functional impairment is highly variable among heterozygous family members.</div></li><li class="half_rhythm"><div>If the <i>BEST1</i> pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be 1% because of the theoretic possibility of parental germline mosaicism [<a class="bibr" href="#bvd.REF.rahbari.2016.126" rid="bvd.REF.rahbari.2016.126">Rahbari et al 2016</a>].</div></li><li class="half_rhythm"><div>If the parents have not been tested for the <i>BEST1</i> pathogenic variant but are clinically unaffected based on electrooculogram (EOG), the risk to sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still at increased risk for BVMD, AVMD, or ADVIRC because of the possibility of reduced penetrance in a heterozygous parent or the theoretic possibility of parental germline mosaicism.</div></li></ul><p><b>Offspring of a proband.</b> Each child of an individual with an autosomal dominant bestrophinopathy has a 50% chance of inheriting the <i>BEST1</i> pathogenic variant.</p><p><b>Other family members.</b> The risk to other family members depends on the status of the proband's parents: if a parent is heterozygous for the <i>BEST1</i> pathogenic variant, the parent's family members are also at risk of having the pathogenic variant.</p></div><div id="bvd.Autosomal_Recessive_Inheritance__Ris"><h3>Autosomal Recessive Inheritance – 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 typically heterozygotes (i.e., carriers of one <i>BEST1</i> pathogenic variant).</div></li><li class="half_rhythm"><div>Accurate recurrence risk counseling relies on carrier testing of both parents to determine if each is heterozygous for a <i>BEST1</i> pathogenic variant. If carrier testing detects the variant in only one parent:</div><ul><li class="half_rhythm"><div>And the child appears to have homozygous <i>BEST1</i> pathogenic variants, possible explanations include a large deletion on one allele (if not previously tested for) and uniparental isodisomy for chromosome 11;</div></li><li class="half_rhythm"><div>And the child has compound heterozygous <i>BEST1</i> pathogenic variants, the child may theoretically have one inherited variant and one <i>de novo</i> pathogenic variant. <i>De novo</i> variants are known to occur at a low but appreciable rate in autosomal recessive disorders [<a class="bibr" href="#bvd.REF.j_nsson.2017.519" rid="bvd.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li></ul></li><li class="half_rhythm"><div>Individuals who are heterozygous for a <i>BEST1</i> variant associated with ARB are generally clinically unaffected [<a class="bibr" href="#bvd.REF.zhao.2012.866" rid="bvd.REF.zhao.2012.866">Zhao et al 2012</a>]. However, mildly diminished responses on multifocal ERG and/or mild symptoms of maculopathy have been reported in several individuals with heterozygous ARB-related <i>BEST1</i> pathogenic variants [<a class="bibr" href="#bvd.REF.macdonald.2012.123" rid="bvd.REF.macdonald.2012.123">MacDonald et al 2012</a>, <a class="bibr" href="#bvd.REF.wivestad_jansson.2016.183" rid="bvd.REF.wivestad_jansson.2016.183">Wivestad Jansson et al 2016</a>].</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>If both parents are known to be heterozygous for a <i>BEST1</i> pathogenic variant, each sib of an affected individual has at conception 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>Individuals who are heterozygous for a <i>BEST1</i> variant associated with ARB are generally clinically unaffected [<a class="bibr" href="#bvd.REF.zhao.2012.866" rid="bvd.REF.zhao.2012.866">Zhao et al 2012</a>]. However, mildly diminished responses on multifocal ERG and/or mild symptoms of maculopathy have been reported in several individuals with heterozygous ARB-related <i>BEST1</i> pathogenic variants [<a class="bibr" href="#bvd.REF.macdonald.2012.123" rid="bvd.REF.macdonald.2012.123">MacDonald et al 2012</a>, <a class="bibr" href="#bvd.REF.wivestad_jansson.2016.183" rid="bvd.REF.wivestad_jansson.2016.183">Wivestad Jansson et al 2016</a>].</div></li></ul><p><b>Offspring of a proband.</b> The offspring of an individual with ARB are obligate heterozygotes for a pathogenic variant in <i>BEST1</i>.</p><p><b>Other family members.</b> Each sib of the proband's parents has a 50% chance of being heterozygous for a <i>BEST1</i> pathogenic variant.</p><div id="bvd.Heterozygote_Detection"><h4>Heterozygote Detection</h4><p>Heterozygote testing for at-risk relatives requires prior identification of the <i>BEST1</i> pathogenic variants in the family.</p></div></div><div id="bvd.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#bvd.Evaluation_of_Relatives_at_Risk">Evaluation of Relatives at Risk</a> for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.</p><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 genetic 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.</div></li></ul></div><div id="bvd.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the <i>BEST1</i> pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. Note: Because intrafamilial clinical variability is observed in the bestrophinopathies, expression and age of onset cannot be predicted on the basis of prenatal molecular genetic test results.</p><p>Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.</p></div></div><div id="bvd.Resources"><h2 id="_bvd_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>Macular Degeneration Foundation</b>
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</div><div>PO Box 531313</div><div>Henderson NV 89053</div><div><b>Phone:</b> 888-633-3937 (toll-free); 702-450-2908</div><div><b>Fax:</b> 702-450-3396</div><div><b>Email:</b> liz@eyesight.org</div><div>
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<a href="http://www.eyesight.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.eyesight.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>National Library of Medicine Genetics Home Reference</b>
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</div><div>
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<a href="https://ghr.nlm.nih.gov/condition/vitelliformmaculardystrophy" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Vitelliform macular dystrophy</a>
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</div></li><li class="half_rhythm"><div>
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<b>NCBI Genes and Disease</b>
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</div><div>
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<a href="/books/NBK22187/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Best disease</a>
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</div></li><li class="half_rhythm"><div>
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<b>Association for Macular Diseases</b>
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</div><div>210 East 64th Street</div><div>8th Floor</div><div>New York NY 10065</div><div><b>Phone:</b> 212-605-3719</div><div><b>Fax:</b> 212-605-3795</div><div><b>Email:</b> association@retinal-research.org</div><div>
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<a href="https://ophthalmicedge.org/patient/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.ophthalmicedge.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><b>Phone:</b> 800-683-5555</div><div>
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<a href="https://www.fightingblindness.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">fightingblindness.org</a>
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</div></li></ul>
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</div><div id="bvd.Molecular_Genetics"><h2 id="_bvd_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="figbvdmolgenTA"><a href="/books/NBK1167/table/bvd.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobbvdmolgenTA"><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="bvd.molgen.TA"><a href="/books/NBK1167/table/bvd.molgen.TA/?report=objectonly" target="object" rid-ob="figobbvdmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Bestrophinopathies: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbvdmolgenTB"><a href="/books/NBK1167/table/bvd.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobbvdmolgenTB"><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="bvd.molgen.TB"><a href="/books/NBK1167/table/bvd.molgen.TB/?report=objectonly" target="object" rid-ob="figobbvdmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Bestrophinopathies (View All in OMIM) </p></div></div><div id="bvd.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p><i>BEST1</i> encodes bestrophin, a chloride ion channel that is sensitive to intracellular calcium [<a class="bibr" href="#bvd.REF.petrukhin.1998.241" rid="bvd.REF.petrukhin.1998.241">Petrukhin et al 1998</a>, <a class="bibr" href="#bvd.REF.sun.2002.4008" rid="bvd.REF.sun.2002.4008">Sun et al 2002</a>]. Bestrophin is highly expressed by the retinal pigment epithelium (RPE) and localizes to the basolateral plasma membrane [<a class="bibr" href="#bvd.REF.marmorstein.2000.12758" rid="bvd.REF.marmorstein.2000.12758">Marmorstein et al 2000</a>]. Bestrophin functions either as a chloride channel or as a regulator of voltage-gated calcium channels in the RPE [<a class="bibr" href="#bvd.REF.hartzell.2008.639" rid="bvd.REF.hartzell.2008.639">Hartzell et al 2008</a>, <a class="bibr" href="#bvd.REF.yu.2008.5660" rid="bvd.REF.yu.2008.5660">Yu et al 2008</a>].</p><p>Expression of disease-associated missense variants causes reduced or abolished membrane current. Bestrophin undergoes dephosphorylation by a protein phosphatase, suggesting that bestrophin participates in a signal transduction pathway that may be related to the modulation of the light peak on electrooculogram [<a class="bibr" href="#bvd.REF.marmorstein.2002.30591" rid="bvd.REF.marmorstein.2002.30591">Marmorstein et al 2002</a>].</p><p><b>Mechanism of disease causation.</b> Loss of function. Pathogenic variants in <i>BEST1</i> alter ion transport by the RPE, resulting in the accumulation of fluid between the RPE and the photoreceptors [<a class="bibr" href="#bvd.REF.qu.2006.5411" rid="bvd.REF.qu.2006.5411">Qu et al 2006</a>, <a class="bibr" href="#bvd.REF.yu.2007.4694" rid="bvd.REF.yu.2007.4694">Yu et al 2007</a>, <a class="bibr" href="#bvd.REF.hartzell.2008.639" rid="bvd.REF.hartzell.2008.639">Hartzell et al 2008</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figbvdTnotablebest1pathogenicvariants"><a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobbvdTnotablebest1pathogenicvariants"><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="bvd.T.notable_best1_pathogenic_variants"><a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object" rid-ob="figobbvdTnotablebest1pathogenicvariants">Table 3. </a></h4><p class="float-caption no_bottom_margin">Notable <i>BEST1</i> Pathogenic Variants </p></div></div></div></div><div id="bvd.Chapter_Notes"><h2 id="_bvd_Chapter_Notes_">Chapter Notes</h2><div id="bvd.Author_History"><h3>Author History</h3><p>Jessica Lawrence, MSc (2020-present)<br />Thomas Lee, MD (2003-present)<br />Ian M MacDonald, MD, CM (2003-present)<br />Dean Y Mah, MSc, MD; University of Alberta (2003-2009)</p></div><div id="bvd.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>16 July 2020 (bp) Comprehensive update posted live</div></li><li class="half_rhythm"><div>12 December 2013 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>7 April 2009 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>8 December 2005 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>27 October 2003 (imd) Revision: sequence analysis clinically available</div></li><li class="half_rhythm"><div>30 September 2003 (me) Review posted live</div></li><li class="half_rhythm"><div>14 July 2003 (imd) Original submission</div></li></ul></div></div><div id="bvd.References"><h2 id="_bvd_References_">References</h2><div id="bvd.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.andrade.2003.1179">Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in best disease. <span><span class="ref-journal">Am J Ophthalmol. </span>2003;<span class="ref-vol">136</span>:1179–81.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14644242" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14644242</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.apushkin.2006.887">Apushkin MA, Fishman GA, Taylor CM, Stone EM. Novel de novo mutation in a patient with Best macular dystrophy. <span><span class="ref-journal">Arch Ophthalmol. </span>2006;<span class="ref-vol">124</span>:887–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16769844" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16769844</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.atchaneeyasakul.2008.139">Atchaneeyasakul LO, Jinda W, Sakolsatayadorn N, Trinavarat A, Ruangvoravate N, Thanasombatskul N, Thongnoppakhun W, Limwongse C. Mutation analysis of the VMD2 gene in Thai families with Best macular dystrophy. <span><span class="ref-journal">Ophthalmic Genet. </span>2008;<span class="ref-vol">29</span>:139–44.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18766995" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18766995</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.bitner.2011.5332">Bitner H, Mizrahi-Meissonnier L, Griefner G, Erdinest I, Sharon D, Banin E. A homozygous frameshift mutation in BEST1 causes the classical form of Best disease in an autosomal recessive mode. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2011;<span class="ref-vol">52</span>:5332–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21467170" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21467170</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.boon.2009.187">Boon CJ, Klevering BJ, Leroy BP, Hoyng CB, Keunen JE, den Hollander AI. The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. <span><span class="ref-journal">Prog Retin Eye Res. </span>2009;<span class="ref-vol">28</span>:187–205.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19375515" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19375515</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.boon.2013.809">Boon CJ, van den Born LI, Visser L, Keunen JE, Bergen AA, Booij JC, Riemslag FC, Florijn RJ, van Schooneveld MJ. Autosomal recessive bestrophinopathy: differential diagnosis and treatment options. <span><span class="ref-journal">Ophthalmology. </span>2013;<span class="ref-vol">120</span>:809–20.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23290749" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23290749</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.clemons.2005.533">Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd, et al. Risk factors for the incidence of advanced age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19. <span><span class="ref-journal">Ophthalmology. </span>2005;<span class="ref-vol">112</span>:533–9.</span> [<a href="/pmc/articles/PMC1513667/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1513667</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15808240" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15808240</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.dalvin.2017.143">Dalvin LA, Pulido JS, Marmorstein AD. Vitelliform dystrophies: prevalence in Olmsted County, Minnesota, United States. <span><span class="ref-journal">Ophthalmic Genet. </span>2017;<span class="ref-vol">38</span>:143–7.</span> [<a href="/pmc/articles/PMC5638045/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5638045</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27120116" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27120116</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.davidson.2009.581">Davidson AE, Millar ID, Urquhart JE, Burgess-Mullan R, Shweikh Y, Parry N, O'Sullivan J, Maher GJ, McKibbin M, Downes SM, Lotery AJ, Jacobson SG, Brown PD, Black GC, Manson FD. Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa. <span><span class="ref-journal">Am J Hum Genet. </span>2009;<span class="ref-vol">85</span>:581–92.</span> [<a href="/pmc/articles/PMC2775838/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2775838</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19853238" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19853238</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.ellingford.2017.719">Ellingford JM, Campbell C, Barton S, Bhaskar S, Gupta S, Taylor RL, Sergouniotis PI, Horn B, Lamb JA, Michaelides M, Webster AR, Newman WG, Panda B, Ramsden SC, Black GC. Validation of copy number variation analysis for next-generation sequencing diagnostics. Version 2. <span><span class="ref-journal">Eur J Hum Genet. </span>2017;<span class="ref-vol">25</span>:719–24.</span> [<a href="/pmc/articles/PMC5427176/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5427176</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28378820" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28378820</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.eksandh.2001.107">Eksandh L, Bakall B, Bauer B, Wadelius C, Andréasson S. Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene. <span><span class="ref-journal">Ophthalmic Genet. </span>2001;<span class="ref-vol">22</span>:107–15.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11449320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11449320</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.glybina.2006.1593">Glybina IV, Frank RN. Localization of multifocal electroretinogram abnormalities to the lesion site: findings in a family with Best disease. <span><span class="ref-journal">Arch Ophthalmol. </span>2006;<span class="ref-vol">124</span>:1593–600.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17102007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17102007</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.hartzell.2008.639">Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT. Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies. <span><span class="ref-journal">Physiol Rev. </span>2008;<span class="ref-vol">88</span>:639–72.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18391176" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18391176</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.iannaccone.2011.211">Iannaccone A, Kerr NC, Kinnick TR, Calzada JI, Stone EM. Autosomal recessive best vitelliform macular dystrophy: report of a family and management of early-onset neovascular complications. <span><span class="ref-journal">Arch Ophthalmol. </span>2011;<span class="ref-vol">129</span>:211–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21320969" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21320969</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.johnson.2017.45">Johnson AA, Guziewicz KE, Lee CJ, Kalathur RC, Pulido JS, Marmorstein LY, Marmorstein AD. Bestrophin 1 and retinal disease. <span><span class="ref-journal">Prog Retin Eye Res. </span>2017;<span class="ref-vol">58</span>:45–69.</span> [<a href="/pmc/articles/PMC5600499/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5600499</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28153808" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28153808</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.j_nsson.2017.519">Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. <span><span class="ref-journal">Nature. </span>2017;<span class="ref-vol">549</span>:519–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28959963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28959963</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.khan.2018.606">Khan KN, Islam F, Moore AT, Michaelides M. The fundus phenotype associated with the p.ala243val best1 mutation. <span><span class="ref-journal">Retina. </span>2018;<span class="ref-vol">38</span>:606–13.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28225368" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28225368</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.kinnick.2011.581">Kinnick TR, Mullins RF, Dev S, Leys M, Mackey DA, Kay CN, Lam BL, Fishman GA, Traboulsi E, Iezzi R, Stone EM. Autosomal recessive vitelliform macular dystrophy in a large cohort of vitelliform macular dystrophy patients. <span><span class="ref-journal">Retina. </span>2011;<span class="ref-vol">31</span>:581–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21273940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21273940</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.leu.2007.1723">Leu J, Schrage NF, Degenring RF. Choroidal neovascularisation secondary to Best's disease in a 13-year-old boy treated by intravitreal bevacizumab. <span><span class="ref-journal">Graefes Arch Clin Exp Ophthalmol. </span>2007;<span class="ref-vol">245</span>:1723–5.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17605026" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17605026</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.li.2006.408">Li Y, Wang G, Dong B, Sun X, Turner MJ, Kamaya S, Zhang K. A novel mutation of the VMD2 gene in a Chinese family with best vitelliform macular dystrophy. <span><span class="ref-journal">Ann Acad Med Singapore. </span>2006;<span class="ref-vol">35</span>:408–10.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16865191" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16865191</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.macdonald.2012.123">MacDonald IM, Gudiseva HV, Villanueva A, Greve M, Caruso R, Ayyagari R. Phenotype and genotype of patients with autosomal recessive bestrophinopathy. <span><span class="ref-journal">Ophthalmic Genet. </span>2012;<span class="ref-vol">33</span>:123–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21809908" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21809908</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.marano.2000.760">Marano F, Deutman AF, Leys A, Aandekerk AL. 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The spectrum of subclinical Best vitelliform macular dystrophy in subjects with mutations in BEST1 gene. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2011;<span class="ref-vol">52</span>:4678–84.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21436265" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21436265</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.querques.2009.2960">Querques G, Zerbib J, Santacroce R, Margaglione M, Delphin N, Rozet JM, Kaplan J, Martinelli D, Delle Noci N, Soubrane G, Souied EH. 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Timing, rates and spectra of human germline mutation. <span><span class="ref-journal">Nat Genet. </span>2016;<span class="ref-vol">48</span>:126–33.</span> [<a href="/pmc/articles/PMC4731925/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4731925</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26656846" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26656846</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.richards.2015.405">Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, et al. 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Topographic mapping of retinal function with the SLO-mfERG under simultaneous control of fixation in Best's disease. <span><span class="ref-journal">Ophthalmologica. </span>2003;<span class="ref-vol">217</span>:154–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12592056" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12592056</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.scholl.2002.1053">Scholl HP, Schuster AM, Vonthein R, Zrenner E. Mapping of retinal function in Best macular dystrophy using multifocal electroretinography. <span><span class="ref-journal">Vision Res. </span>2002;<span class="ref-vol">42</span>:1053–61.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11934455" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11934455</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.stenson.2020.1197">Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN. The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting. <span><span class="ref-journal">Hum Genet. </span>2020;<span class="ref-vol">139</span>:1197–207.</span> [<a href="/pmc/articles/PMC7497289/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7497289</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32596782" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32596782</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.sun.2002.4008">Sun H, Tsunenari T, Yau KW, Nathans J. The vitelliform macular dystrophy protein defines a new family of chloride channels. <span><span class="ref-journal">Proc Natl Acad Sci U S A. </span>2002;<span class="ref-vol">99</span>:4008–13.</span> [<a href="/pmc/articles/PMC122639/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC122639</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11904445" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11904445</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.testa.2008.1467">Testa F, Rossi S, Passerini I, Sodi A, Di Iorio V, Interlandi E, Della Corte M, Menchini U, Rinaldi E, Torricelli F, Simonelli F. A normal electro-oculography in a family affected by Best disease with a novel spontaneous mutation of the BEST1 gene. <span><span class="ref-journal">Br J Ophthalmol. </span>2008;<span class="ref-vol">92</span>:1467–70.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/18703557" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18703557</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.van_schil.2018.202">Van Schil K, Naessens S, Van de Sompele S, Carron M, Aslanidis A, Van Cauwenbergh C, Kathrin Mayer A, Van Heetvelde M, Bauwens M, Verdin H, Coppieters F, Greenberg ME, Yang MG, Karlstetter M, Langmann T, De Preter K, Kohl S, Cherry TJ, Leroy BP, De Baere E, et al. Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations. <span><span class="ref-journal">Genet Med. </span>2018;<span class="ref-vol">20</span>:202–13.</span> [<a href="/pmc/articles/PMC5787040/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5787040</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28749477" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28749477</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.wivestad_jansson.2016.183">Wivestad Jansson R, Berland S, Bredrup C, Austeng D, Andréasson S, Wittström E. Biallelic mutations in the BEST1 gene: additional families with autosomal recessive bestrophinopathy. <span><span class="ref-journal">Ophthalmic Genet. </span>2016;<span class="ref-vol">37</span>:183–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26333019" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26333019</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.yardley.2004.3683">Yardley J, Leroy BP, Hart-Holden N, Lafaut BA, Loeys B, Messiaen LM, Perveen R, Reddy MA, Bhattacharya SS, Traboulsi E, Baralle D, De Laey JJ, Puech B, Kestelyn P, Moore AT, Manson FD, Black GC. Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2004;<span class="ref-vol">45</span>:3683–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15452077" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15452077</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.yu.2007.4694">Yu K, Qu Z, Cui Y, Hartzell HC. Chloride channel activity of bestrophin mutants associated with mild or late-onset macular degeneration. <span><span class="ref-journal">Invest Ophthalmol Vis Sci. </span>2007;<span class="ref-vol">48</span>:4694–705.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/17898294" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17898294</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.yu.2008.5660">Yu K, Xiao Q, Cui G, Lee A, Hartzell HC. The Best disease-linked Cl- channel hBest1 regulates Ca V 1 (L-type) Ca2+ channels via src-homology-binding domains. <span><span class="ref-journal">J Neurosci. </span>2008;<span class="ref-vol">28</span>:5660–70.</span> [<a href="/pmc/articles/PMC2587081/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2587081</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18509027" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18509027</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="bvd.REF.zhao.2012.866">Zhao L, Grob S, Corey R, Krupa M, Luo J, Du H, Lee C, Hughes G, Lee J, Quach J, Zhu J, Shaw PX, Kozak I, Zhang K. A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy. <span><span class="ref-journal">Eye (Lond). </span>2012;<span class="ref-vol">26</span>:866–71.</span> [<a href="/pmc/articles/PMC3376281/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3376281</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22422030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22422030</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1167_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Ian M MacDonald</span>, MDCM, MSc<div class="affiliation small">Department of Ophthalmology
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University of Alberta<br />Edmonton, Alberta, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.atreblau@lanodcam" class="oemail">ac.atreblau@lanodcam</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Thomas Lee</span>, MD, MSc<div class="affiliation small">Department of Ophthalmology
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University of Ottawa<br />Ottawa, Ontario, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.no.hot@eelsamoht" class="oemail">ac.no.hot@eelsamoht</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Jessica Lawrence</span>, MSc<div class="affiliation small">Alberta Health Services<br />Edmonton, Alberta, Canada<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="ac.sha@2ecnerwal.acissej" class="oemail">ac.sha@2ecnerwal.acissej</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">September 30, 2003</span>; Last Update: <span itemprop="dateModified">July 16, 2020</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © 1993-2025, University of Washington, Seattle. GeneReviews is
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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>MacDonald IM, Lee T, Lawrence J. Bestrophinopathies. 2003 Sep 30 [Updated 2020 Jul 16]. 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/bscl/?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/bpan/?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="figobbvdTc"><div id="bvd.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1167/table/bvd.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bvd.Tc_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bvd.Tc_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bestrophinopathies: Included Phenotypes</th></tr></thead><tbody><tr><td headers="hd_h_bvd.Tc_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Best vitelliform macular dystrophy (BVMD)</div></li><li class="half_rhythm"><div>Adult-onset vitelliform macular dystrophy (AVMD)</div></li><li class="half_rhythm"><div>Autosomal dominant vitreoretinochoroidopathy (ADVIRC)</div></li><li class="half_rhythm"><div>Autosomal recessive bestrophinopathy (ARB)</div></li></ul>
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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">For synonyms and outdated names, see <a href="#bvd.Prevalence">Nomenclature</a>.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbvdTmoleculargenetictestingusedin"><div id="bvd.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 Bestrophinopathies</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1167/table/bvd.T.molecular_genetic_testing_used_in/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bvd.T.molecular_genetic_testing_used_in_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene <sup>1</sup></th><th id="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Method</th><th id="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Proportion of Probands with a Pathogenic Variant <sup>2</sup> Detectable by Method</th></tr></thead><tbody><tr><td headers="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>BEST1</i>
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</td><td headers="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>3</sup></td><td headers="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>99% <sup>4</sup></td></tr><tr><td headers="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>5</sup></td><td headers="hd_h_bvd.T.molecular_genetic_testing_used_in_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare <sup>4</sup></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="bvd.TF.1.1"><p class="no_margin">See <a href="/books/NBK1167/?report=reader#bvd.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="bvd.TF.1.2"><p class="no_margin">See <a href="#bvd.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in this gene.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="bvd.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="bvd.TF.1.4"><p class="no_margin"><a class="bibr" href="#bvd.REF.boon.2009.187" rid="bvd.REF.boon.2009.187">Boon et al [2009]</a>, <a class="bibr" href="#bvd.REF.kinnick.2011.581" rid="bvd.REF.kinnick.2011.581">Kinnick et al [2011]</a>, and data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#bvd.REF.stenson.2020.1197" rid="bvd.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="bvd.TF.1.5"><p class="no_margin">Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.</p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="bvd.TF.1.6"><p class="no_margin"><a class="bibr" href="#bvd.REF.boon.2013.809" rid="bvd.REF.boon.2013.809">Boon et al [2013]</a>, <a class="bibr" href="#bvd.REF.ellingford.2017.719" rid="bvd.REF.ellingford.2017.719">Ellingford et al [2017]</a>, <a class="bibr" href="#bvd.REF.van_schil.2018.202" rid="bvd.REF.van_schil.2018.202">Van Schil et al [2018]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobbvdTbestrophinopathiesfrequencyofph"><div id="bvd.T.bestrophinopathies_frequency_of_ph" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Bestrophinopathies: Frequency of Phenotypes</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1167/table/bvd.T.bestrophinopathies_frequency_of_ph/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bvd.T.bestrophinopathies_frequency_of_ph_lrgtbl__"><table><thead><tr><th id="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_1" style="text-align:left;vertical-align:middle;">Phenotype</th><th id="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2" colspan="3" scope="colgroup" rowspan="1" style="text-align:center;vertical-align:middle;">Ophthalmologic Findings</th><th id="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_3" style="text-align:left;vertical-align:middle;">Comment</th></tr><tr><th headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2" id="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Most Common</th><th headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2" id="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Common</th><th headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2" id="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Infrequent</th></tr></thead><tbody><tr><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">BVMD</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">"Egg yolk"-like vitelliform lesion</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Multiple vitelliform lesions</div></li><li class="half_rhythm"><div>Atrophic scar</div></li></ul>
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</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Choroidal neovascularization</div></li><li class="half_rhythm"><div>Unilateral vitelliform lesions</div></li></ul>
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</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Vitelliform lesion progressing through stages of heterogeneous "scramble egg" to pseudohypopyon lesion to atrophic scar</div></li><li class="half_rhythm"><div>Visual acuity can progress from 20/20 to <20/200.</div></li></ul>
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</td></tr><tr><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">AVMD</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bilateral, small, circular vitelliform lesion</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Atrophic scar</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Choroidal neovascularization</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Lesions ↑ & then ↓ in size, becoming an atrophic area.</div></li><li class="half_rhythm"><div>Visual acuity 20/40 to 20/200</div></li></ul>
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</td></tr><tr><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ADVIRC</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Peripheral chorioretinal atrophy w/white retinal opacities</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Hyperopia</div></li><li class="half_rhythm"><div>Shallow anterior chamber/angle closure</div></li><li class="half_rhythm"><div>Microcornea</div></li><li class="half_rhythm"><div>Fibrillar vitreous condensation</div></li></ul>
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</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Breakdown of blood-retinal barrier w/retinal neovascularization</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ARB</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>White subretinal deposits</div></li><li class="half_rhythm"><div>Subretinal fluid</div></li><li class="half_rhythm"><div>Hyperopia</div></li></ul>
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</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Subretinal fibrous scars</div></li><li class="half_rhythm"><div>Shallow anterior chamber/angle closure</div></li><li class="half_rhythm"><div>Glaucoma</div></li><li class="half_rhythm"><div>Cystoid macular edema</div></li></ul>
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</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_2 hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_2_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Choroidal neovascularization</td><td headers="hd_h_bvd.T.bestrophinopathies_frequency_of_ph_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Subretinal deposits w/subretinal fluid in early stages progressing to subretinal fibrosis</div></li><li class="half_rhythm"><div>Visual acuity can progress from 20/20 to <20/200.</div></li></ul>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobbvdmolgenTA"><div id="bvd.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Bestrophinopathies: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1167/table/bvd.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bvd.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_bvd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_bvd.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_bvd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_bvd.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_bvd.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_bvd.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_bvd.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="/gene/7439" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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<i>BEST1</i>
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</a>
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</td><td headers="hd_b_bvd.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=7439" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">11q12<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_b_bvd.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.uniprot.org/uniprot/O76090" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Bestrophin-1</a>
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</td><td headers="hd_b_bvd.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://databases.lovd.nl/shared/genes/BEST1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BEST1 gene homepage</a>
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</td><td headers="hd_b_bvd.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=BEST1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BEST1</a>
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</td><td headers="hd_b_bvd.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=BEST1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">BEST1</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="bvd.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="figobbvdmolgenTB"><div id="bvd.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Bestrophinopathies (<a href="/omim/153700,193220,607854,611809" 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/NBK1167/table/bvd.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bvd.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/153700" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">153700</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MACULAR DYSTROPHY, VITELLIFORM, 2; VMD2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/193220" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">193220</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VITREORETINOCHOROIDOPATHY; VRCP</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/607854" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">607854</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BESTROPHIN 1; BEST1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/611809" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611809</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">BESTROPHINOPATHY, AUTOSOMAL RECESSIVE; ARB</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobbvdTnotablebest1pathogenicvariants"><div id="bvd.T.notable_best1_pathogenic_variants" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Notable <i>BEST1</i> Pathogenic Variants</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1167/table/bvd.T.notable_best1_pathogenic_variants/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__bvd.T.notable_best1_pathogenic_variants_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference<br />Sequences</th><th id="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide<br />Change</th><th id="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004183.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004183<wbr style="display:inline-block"></wbr>​.3</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_004174.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_004174<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.383G>C</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Trp93Cys</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persons who trace their ancestry to a large Swedish kindred [<a class="bibr" href="#bvd.REF.petrukhin.1998.241" rid="bvd.REF.petrukhin.1998.241">Petrukhin et al 1998</a>] <sup>1</sup></td></tr><tr><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.266T>C</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val89Ala</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_4" rowspan="3" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/mild or late-onset disease (See <a href="#bvd.GenotypePhenotype_Correlations">Genotype-Phenotype Correlations</a>.)</td></tr><tr><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.679T>A</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Tyr227Asn</td></tr><tr><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.728C>T</td><td headers="hd_h_bvd.T.notable_best1_pathogenic_variants_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ala243Val</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="bvd.TF.3.1"><p class="no_margin">Described as "pedigree S1" [<a class="bibr" href="#bvd.REF.petrukhin.1998.241" rid="bvd.REF.petrukhin.1998.241">Petrukhin et al 1998</a>]</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobbvdF1"><div id="bvd.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1167/bin/bvd-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Best vitelliform macular dystrophy: Vitelliform stage (Stage 2)</p></div></div></article><article data-type="fig" id="figobbvdF2"><div id="bvd.F2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1167/bin/bvd-Image002.jpg" alt="Figure 2. " /></div><h3><span class="label">Figure 2. </span></h3><div class="caption"><p>Best vitelliform macular dystrophy: Pseudohypopyon (Stage 3)</p></div></div></article><article data-type="fig" id="figobbvdF3"><div id="bvd.F3" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1167/bin/bvd-Image003.jpg" alt="Figure 3. " /></div><h3><span class="label">Figure 3. </span></h3><div class="caption"><p>Best vitelliform macular dystrophy: Central scarring (Stage 4b)</p></div></div></article><article data-type="fig" id="figobbvdF4"><div id="bvd.F4" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1167/bin/bvd-Image004.jpg" alt="Figure 4. " /></div><h3><span class="label">Figure 4. </span></h3><div class="caption"><p>Right eye of a male age 72 years with molecularly confirmed Best disease</p><p>A. Macula shows loss of photoreceptor cells and an attenuated outer plexiform layer (OPL).</p><p>B & C. Fovea shows deposits of PAS-positive material and pigment granules (arrows) without underlying RPE cells.</p><p>D. Hyperpigmentation of the RPE (red arrows) is seen in the perifovea.</p><p>Image courtesy of C-C Chan, National Eye Institute, NIH, retired</p></div></div></article><article data-type="fig" id="figobbvdF5"><div id="bvd.F5" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1167/bin/bvd-Image005.jpg" alt="Figure 5. " /></div><h3><span class="label">Figure 5. </span></h3><div class="caption"><p>Left eye of the same individual</p><p>A. Macula shows loss of photoreceptor cells and attenuated OPL.</p><p>B & C. Fovea shows a small disciform scar of thin fibrous tissue containing PAS-positive material (arrows) without underlying RPE cells.</p><p>D. Hyperpigmentation of RPE (red arrows) is noted in the perifovea.</p><p>Image courtesy of C-C Chan, National Eye Institute, NIH, retired</p></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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