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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Xeroderma Pigmentosum - GeneReviews® - NCBI Bookshelf</title>
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<meta name="citation_title" content="Xeroderma Pigmentosum">
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<meta name="citation_publisher" content="University of Washington, Seattle">
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<meta name="citation_date" content="2022/03/24">
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<meta name="citation_author" content="Kenneth H Kraemer">
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<meta name="citation_author" content="John J DiGiovanna">
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<meta name="citation_author" content="Deborah Tamura">
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<meta name="citation_keywords" content="DNA excision repair protein ERCC-1">
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<meta name="citation_keywords" content="DNA excision repair protein ERCC-5">
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<meta name="citation_keywords" content="DNA polymerase eta">
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<meta name="citation_keywords" content="DNA repair endonuclease XPF">
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<meta name="citation_keywords" content="DNA repair protein complementing XP-A cells">
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<meta name="citation_keywords" content="General transcription and DNA repair factor IIH helicase subunit XPD">
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<meta name="citation_keywords" content="XPA">
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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="_NBK1397_"><span class="title" itemprop="name">Xeroderma Pigmentosum</span></h1><p class="contribs">Kraemer KH, DiGiovanna JJ, Tamura D.</p><p class="fm-aai"><a href="#_NBK1397_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 38 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="xp.Summary" itemprop="description"><h2 id="_xp_Summary_">Summary</h2><div><h4 class="inline">Clinical characteristics.</h4><p>Xeroderma pigmentosum (XP) is characterized by:</p><ul><li class="half_rhythm"><div>Acute sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure) with marked freckle-like pigmentation of the face before age two years;</div></li><li class="half_rhythm"><div>Sunlight-induced ocular involvement (photophobia, severe keratitis, atrophy of the skin of the lids, ocular surface neoplasms);</div></li><li class="half_rhythm"><div>Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma) within the first decade of life.</div></li></ul><p>Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, progressive cognitive impairment, and ataxia). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).</p></div><div><h4 class="inline">Diagnosis/testing.</h4><p>The diagnosis of XP is established in a proband on the basis of clinical findings and family history and/or by the identification of biallelic pathogenic variants in <i>DDB2</i>, <i>ERCC1</i>, <i>ERCC2</i>, <i>ERCC3</i>, <i>ERCC4</i>, <i>ERCC5</i>, <i>POLH</i>, <i>XPA</i>, or <i>XPC</i>.</p></div><div><h4 class="inline">Management.</h4><p><i>Treatment of manifestations:</i> Premalignant skin lesions such as actinic keratoses can be treated by freezing with liquid nitrogen; larger areas can be treated with field treatments such as topical 5-fluorouracil or imiquimod preparations. Rarely, therapeutic dermatome shaving or dermabrasion has been used; skin neoplasms can be treated (as in persons without XP) with electrodesiccation and curettage or surgical excision; skin cancers that are recurrent or in locations at high risk for recurrence are best treated with Mohs micrographic surgery. Oral isotretinoin or acitretin can prevent new skin neoplasms but have many side effects. Neoplasms of the eyelids, conjunctiva, and cornea can be treated surgically; corneal injury associated with eyelid abnormality can be decreased with eye drops or soft contact lenses; corneal transplantation may improve the visual impairment resulting from severe keratitis. Hearing loss may be treated with hearing aids.</p><p><i>Prevention of primary manifestations:</i> Avoid sun and other UV exposure to the skin and eyes. Measure UV light with a light meter in an affected individual's home, school, and/or work environment so that high levels of environmental UV can be identified and eliminated.</p><p><i>Surveillance:</i> Skin examinations by a physician every three to 12 months; eye exams for signs of UV exposure and damage every six months; routine eye and neurologic examinations for progressive neurologic abnormalities every 12 months; audiograms every six to12 months.</p><p><i>Agents/circumstances to avoid:</i> UV exposure from sunlight and artificial sources of UV radiation; cigarette smoke.</p><p><i>Evaluation of relatives at risk:</i> If family-specific pathogenic variants have been identified, molecular genetic testing of at-risk sibs can permit early diagnosis and rigorous sun protection from an early age.</p><p><i>Pregnancy management</i>: Systemic retinoids (isotretinoin, acitretin) may be used as skin cancer chemopreventive agents. These drugs are known to be teratogenic to a developing fetus and pose a high risk for birth defects. Women of reproductive age who are taking a systemic retinoid must use effective contraception and be monitored with regular pregnancy tests.</p></div><div><h4 class="inline">Genetic counseling.</h4><p>XP is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an XP-related 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. Once the XP-related pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for XP are possible.</p></div></div><div id="xp.Diagnosis"><h2 id="_xp_Diagnosis_">Diagnosis</h2><p><a class="bibr" href="#xp.REF.moriwaki.2017.1087" rid="xp.REF.moriwaki.2017.1087">Moriwaki et al [2017]</a> (<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/1346-8138.13907" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>) published diagnostic criteria focused on Japanese individuals with xeroderma pigmentosum (XP).</p><div id="xp.Suggestive_Findings"><h3>Suggestive Findings</h3><p>XP <b>should be suspected</b> in individuals with the following clinical findings and family history.</p><p>
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<b>Clinical findings</b>
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</p><ul><li class="half_rhythm"><div>
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<b>Skin</b>
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</div><ul><li class="half_rhythm"><div>Acute sun sensitivity (severe sunburn with blistering or persistent erythema on minimal sun exposure)</div></li><li class="half_rhythm"><div>Marked freckle-like pigmentation (lentigos) on the face before age two years</div></li><li class="half_rhythm"><div>Skin cancer within the first decade of life</div></li></ul></li><li class="half_rhythm"><div>
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<b>Eye</b>
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</div><ul><li class="half_rhythm"><div>Photophobia with prominent conjunctival injection</div></li><li class="half_rhythm"><div>Severe keratitis, sometimes resulting in corneal opacification and vascularization</div></li><li class="half_rhythm"><div>Increased pigmentation of the lids with loss of lashes</div></li><li class="half_rhythm"><div>Atrophy of the skin of the lids resulting in ectropion, entropion, or in severe cases complete loss of the lids</div></li><li class="half_rhythm"><div>Ocular surface neoplasms</div></li></ul></li><li class="half_rhythm"><div>
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<b>Nervous system</b>
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</div><ul><li class="half_rhythm"><div>Diminished or absent deep tendon stretch reflexes. EMG and nerve conduction velocities may show an axonal (or mixed) neuropathy.</div></li><li class="half_rhythm"><div>Progressive sensorineural hearing loss. Audiometry may reveal early high-tone hearing loss.</div></li><li class="half_rhythm"><div>Acquired microcephaly. CT and MRI of the brain may show enlarged ventricles with thinning of the cortex and thickening of the bones of the skull.</div></li><li class="half_rhythm"><div>Progressive cognitive impairment</div></li><li class="half_rhythm"><div>Ataxia</div></li></ul></li></ul><p><b>Family history</b> is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.</p></div><div id="xp.Establishing_the_Diagnosis"><h3>Establishing the Diagnosis</h3><p>The diagnosis of XP <b>is established</b> in a proband on the basis of clinical findings and family history (see <a href="#xp.Suggestive_Findings">Suggestive Findings</a>) and/or by the identification of biallelic pathogenic variants in one of the genes listed in <a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object" rid-ob="figobxpTmoleculargenetictestingusedinx">Table 1</a>.</p><p>Molecular genetic testing approaches can include a combination of <b>gene-targeted testing</b> (multigene panel) and <b>comprehensive</b>
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<b>genomic testing</b> (exome sequencing, 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="#xp.Suggestive_Findings">Suggestive Findings</a> are likely to be diagnosed using gene-targeted testing (see <a href="#xp.Option_1">Option 1</a>), whereas those in whom the diagnosis of XP has not been considered are more likely to be diagnosed using genomic testing (see <a href="#xp.Option_2">Option 2</a>).</p><div id="xp.Option_1"><h4>Option 1</h4><p><b>A xeroderma pigmentosum</b>
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<b>multigene panel</b> that includes all of the genes listed in <a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object" rid-ob="figobxpTmoleculargenetictestingusedinx">Table 1</a> and other genes of interest (see <a href="#xp.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="xp.Option_2"><h4>Option 2</h4><p><b>Comprehensive</b>
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<b>genomic testing</b> does not require the clinician to determine which gene(s) are likely involved. <b>Exome sequencing</b> is most commonly used; <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><p>NOTE: Some regions of the world have increased prevalence of XP and the proportion of XP attributed to pathogenic variants in a specific gene may vary by country of origin of the proband associated with particular founder variants in that region. See <a href="#xp.Prevalence">Prevalence</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTmoleculargenetictestingusedinx"><a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object" title="Table 1. " class="img_link icnblk_img" rid-ob="figobxpTmoleculargenetictestingusedinx"><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="xp.T.molecular_genetic_testing_used_in_x"><a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object" rid-ob="figobxpTmoleculargenetictestingusedinx">Table 1. </a></h4><p class="float-caption no_bottom_margin">Molecular Genetic Testing Used in Xeroderma Pigmentosum </p></div></div></div></div></div><div id="xp.Clinical_Characteristics"><h2 id="_xp_Clinical_Characteristics_">Clinical Characteristics</h2><div id="xp.Clinical_Description"><h3>Clinical Description</h3><p>The findings from 106 individuals with XP examined at the National Institutes of Health (US) in a long-term study from 1971 to 2009 by <a class="bibr" href="#xp.REF.bradford.2011.168" rid="xp.REF.bradford.2011.168">Bradford et al [2011]</a> and <a class="bibr" href="#xp.REF.fassihi.2016.e1236" rid="xp.REF.fassihi.2016.e1236">Fassihi et al [2016]</a> are summarized in <a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_frequency_of/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumfrequencyof">Table 2</a> and the text following.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTxerodermapigmentosumfrequencyof"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_frequency_of/?report=objectonly" target="object" title="Table 2. " class="img_link icnblk_img" rid-ob="figobxpTxerodermapigmentosumfrequencyof"><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="xp.T.xeroderma_pigmentosum_frequency_of"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_frequency_of/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumfrequencyof">Table 2. </a></h4><p class="float-caption no_bottom_margin">Xeroderma Pigmentosum: Frequency of Select Features </p></div></div><p><b>Cutaneous findings.</b> More than half of individuals with XP have a history of acute sunburn reaction on minimal UV exposure. The remainder of individuals with XP tan without excessive burning [<a class="bibr" href="#xp.REF.sethi.2013.1279" rid="xp.REF.sethi.2013.1279">Sethi et al 2013</a>]. In all individuals, numerous freckle-like hyperpigmented macules appear on sun-exposed skin.</p><ul><li class="half_rhythm"><div>The median onset of the cutaneous symptoms is between ages one and two years.</div></li><li class="half_rhythm"><div>These abnormalities are limited to sun-exposed areas.</div></li><li class="half_rhythm"><div>Continued sun exposure causes the skin to become dry and parchment-like with increased pigmentation; hence the name xeroderma pigmentosum ("dry pigmented skin").</div></li><li class="half_rhythm"><div>Most individuals with XP develop xerosis (dry skin) and poikiloderma (the constellation of hyper- and hypopigmentation, atrophy, and telangiectasia).</div></li><li class="half_rhythm"><div>Premalignant actinic keratoses develop at an early age.</div></li><li class="half_rhythm"><div>XP is an example of accelerated photoaging. The appearance of sun-exposed skin in children with XP is similar to that occurring in farmers and sailors after many years of extreme sun exposure [<a class="bibr" href="#xp.REF.rizza.2021.976" rid="xp.REF.rizza.2021.976">Rizza et al 2021</a>].</div></li></ul><p><b>Ocular abnormalities</b> are almost as common as the cutaneous abnormalities [<a class="bibr" href="#xp.REF.brooks.2013.1324" rid="xp.REF.brooks.2013.1324">Brooks et al 2013</a>]. Beginning in the first decade of life, findings are usually limited to the anterior, UV-exposed portions of the eyes including the conjunctiva, cornea, and lids.</p><ul><li class="half_rhythm"><div>Dry eyes are a common finding in XP and may be seen in patients in the first decade of life.</div></li><li class="half_rhythm"><div>Epithelioma, squamous cell carcinoma, and melanoma of UV-exposed portions of the eye are common.</div></li><li class="half_rhythm"><div>The ocular manifestations may be more severe in heavily pigmented individuals.</div></li><li class="half_rhythm"><div>Benign conjunctival inflammatory masses that develop can spread to obscure the cornea [<a class="bibr" href="#xp.REF.mahindra.2008.881" rid="xp.REF.mahindra.2008.881">Mahindra et al 2008</a>].</div></li><li class="half_rhythm"><div>Corneal findings include photophobia, severe keratitis, corneal opacification, and neovascularization.</div></li><li class="half_rhythm"><div>Lid findings include atrophy of the skin of the lids resulting in ectropion, entropion, or (in severe cases) complete loss of the lids. Lentigines, freckling on the lids, and lash loss are also common findings.</div></li></ul><p><b>Neurologic findings.</b> Progressive neurologic abnormalities that worsen slowly were reported in approximately 25% of 106 affected individuals.</p><ul><li class="half_rhythm"><div>The onset may be early in infancy or, in some individuals, delayed until the second decade or later [<a class="bibr" href="#xp.REF.rapin.2000.1442" rid="xp.REF.rapin.2000.1442">Rapin et al 2000</a>, <a class="bibr" href="#xp.REF.shanbhag.2018.e240" rid="xp.REF.shanbhag.2018.e240">Shanbhag et al 2018</a>].</div></li><li class="half_rhythm"><div>The neurologic abnormalities may be mild (e.g., isolated hyporeflexia) or severe, including acquired microcephaly, progressive intellectual impairment, sensorineural hearing loss beginning with high frequencies, spasticity, ataxia, and/or seizures.</div></li><li class="half_rhythm"><div>During an upper respiratory infection some individuals may develop difficulty swallowing or, rarely, vocal cord paralysis [<a class="bibr" href="#xp.REF.ohto.2004.222" rid="xp.REF.ohto.2004.222">Ohto et al 2004</a>].</div></li><li class="half_rhythm"><div>Reduced nerve conduction velocity may also be present on nerve conduction studies [<a class="bibr" href="#xp.REF.lehky.2021.393" rid="xp.REF.lehky.2021.393">Lehky et al 2021</a>].</div></li></ul><p><b>Cutaneous neoplasia.</b> If aggressive UV avoidance is not begun early, accumulated sunlight-induced DNA damage is likely to result in skin cancer within the first decade of life. <a class="bibr" href="#xp.REF.bradford.2011.168" rid="xp.REF.bradford.2011.168">Bradford et al [2011]</a> found that individuals with XP younger than age 20 years were at increased risk for the following cancers:</p><ul><li class="half_rhythm"><div class="half_rhythm"><b>Non-melanoma (basal cell and squamous cell) skin cancer</b> at UV-exposed sites. The >10,000-fold increased risk was associated with a median age of onset of nine years, nearly 60 years earlier than in the US general population.</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Cutaneous melanoma.</b> The >2,000-fold increased risk was associated with a median age of onset of 22 years, more than 30 years earlier than in the US general population.</div><div class="half_rhythm">Surprisingly, those with XP who had the most severe sun sensitivity had a later onset of skin cancer – perhaps because they used greater sun protection.</div></li></ul><p>
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<b>Other neoplasias</b>
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</p><ul><li class="half_rhythm"><div>A substantial number of people with XP have oral cavity neoplasms, particularly squamous cell carcinoma of the tip of the tongue, a presumed sun-exposed location [<a class="bibr" href="#xp.REF.kraemer.1994.1018" rid="xp.REF.kraemer.1994.1018">Kraemer et al 1994</a>, <a class="bibr" href="#xp.REF.butt.2010.534" rid="xp.REF.butt.2010.534">Butt et al 2010</a>].</div></li><li class="half_rhythm"><div>Gliomas of the brain and spinal cord, tumors of the lung, uterus, breast, pancreas, stomach, kidney, and testicles, and leukemia have been reported in a few individuals with XP [<a class="bibr" href="#xp.REF.digiovanna.1998.153" rid="xp.REF.digiovanna.1998.153">DiGiovanna et al 1998</a>, <a class="bibr" href="#xp.REF.bradford.2011.168" rid="xp.REF.bradford.2011.168">Bradford et al 2011</a>, <a class="bibr" href="#xp.REF.lai.2013.4" rid="xp.REF.lai.2013.4">Lai et al 2013</a>, <a class="bibr" href="#xp.REF.fassihi.2016.e1236" rid="xp.REF.fassihi.2016.e1236">Fassihi et al 2016</a>, <a class="bibr" href="#xp.REF.sarasin.2019b.2718" rid="xp.REF.sarasin.2019b.2718">Sarasin et al 2019b</a>, <a class="bibr" href="#xp.REF.oetjen.2020.e144" rid="xp.REF.oetjen.2020.e144">Oetjen et al 2020</a>].</div></li><li class="half_rhythm"><div>Because some of the carcinogens in cigarette smoke bind to DNA, resulting in damage that is repaired by the nucleotide excision repair system, this unrepaired DNA damage may contribute to the development of lung cancer in individuals with XP who smoke. The risk for lung cancer due to exposure from secondhand smoke has not been determined.</div></li></ul><p>Overall, there is an estimated 34-fold increase in internal neoplasms in XP, and tumors arise 50 years earlier compared to the US general population [<a class="bibr" href="#xp.REF.nikolaev.2022.104" rid="xp.REF.nikolaev.2022.104">Nikolaev et al 2022</a>].</p><p>
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<b>Other medical concerns</b>
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</p><ul><li class="half_rhythm"><div>Women with XP are at increased risk for premature menopause (menopause before age 40 years) and may require assisted reproductive technology to experience pregnancy [Authors, personal communication]. A study of reproductive health in women with XP identified premature menopause in 31% of the participants, the majority of whom had pathogenic variants in <i>XPC</i> [<a class="bibr" href="#xp.REF.merideth.2019.814" rid="xp.REF.merideth.2019.814">Merideth et al 2019</a>].</div></li><li class="half_rhythm"><div>Individuals with XP are at risk for thyroid nodules and carcinoma. <a class="bibr" href="#xp.REF.kouatcheu.2021.1475" rid="xp.REF.kouatcheu.2021.1475">Kouatcheu et al [2021]</a> reported on 29 individuals seen prospectively as part of a natural history study and found that 18 had thyroid nodules and two were diagnosed with papillary thyroid cancer. In addition, researchers studying XP in northern Africa have noted thyroid nodules and thyroid cancer in multiple individuals with XP [<a class="bibr" href="#xp.REF.ben_rekaya.2013.316286" rid="xp.REF.ben_rekaya.2013.316286">Ben Rekaya et al 2013</a>, <a class="bibr" href="#xp.REF.hadjrabia.2013.1109" rid="xp.REF.hadjrabia.2013.1109">Hadj-Rabia et al 2013</a>, <a class="bibr" href="#xp.REF.jerbi.2016.439" rid="xp.REF.jerbi.2016.439">Jerbi et al 2016</a>]. A 74-fold increased frequency of thyroid cancers was estimated by <a class="bibr" href="#xp.REF.nikolaev.2022.104" rid="xp.REF.nikolaev.2022.104">Nikolaev et al [2022]</a>.</div></li></ul><p><b>Life span.</b> The median age at death (29 years) in persons with XP with neurodegeneration was younger than that in persons with XP without neurodegeneration (37 years) (p=0.02). The three most common causes of death were skin cancer, neurologic degeneration, and internal cancer [<a class="bibr" href="#xp.REF.bradford.2011.168" rid="xp.REF.bradford.2011.168">Bradford et al 2011</a>]. Early diagnosis and use of sun protection have been shown to extend the life span in Japanese patients [<a class="bibr" href="#xp.REF.nakano.2016.28" rid="xp.REF.nakano.2016.28">Nakano et al 2016</a>].</p></div><div id="xp.Phenotype_Correlations_by_Gene"><h3>Phenotype Correlations by Gene</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTxerodermapigmentosumphenotypecor"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_phenotype_cor/?report=objectonly" target="object" title="Table 3. " class="img_link icnblk_img" rid-ob="figobxpTxerodermapigmentosumphenotypecor"><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="xp.T.xeroderma_pigmentosum_phenotype_cor"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_phenotype_cor/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumphenotypecor">Table 3. </a></h4><p class="float-caption no_bottom_margin">Xeroderma Pigmentosum: Phenotype Correlations by Gene </p></div></div></div><div id="xp.GenotypePhenotype_Correlations"><h3>Genotype-Phenotype Correlations</h3><p>No genotype-phenotype correlations, besides those shown in <a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_phenotype_cor/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumphenotypecor">Table 3</a>, have been identified.</p></div><div id="xp.Nomenclature"><h3>Nomenclature</h3><p>Xeroderma pigmentosum was first described in Vienna by Moriz Kaposi in the textbook of dermatology he published in 1870 with his father-in-law, Ferdinand Hebra. The disorder was first called xeroderma or parchment skin. See discussion in <a class="bibr" href="#xp.REF.kraemer.1987.241" rid="xp.REF.kraemer.1987.241">Kraemer et al [1987]</a> and in <a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer [2012]</a>.</p><p>Previously, an individual with XP with any neurologic abnormality was said to have DeSanctis-Cacchione syndrome. With clarification of the spectrum of XP disease, this term is now reserved for XP with severe neurologic disease, dwarfism, and immature sexual development. The complete DeSanctis-Cacchione syndrome has been recognized in very few individuals; however, many individuals with XP have one or more of its neurologic features.</p><p>"Pigmented xerodermoid" is now known to be identical to the XP variant.</p><p>Before the genes responsible for XP were identified, complementation groups were used to categorize functional defects in affected individuals. In an XP complementation analysis, cells from affected individuals were fused in the laboratory to determine whether their defects were different, in which case they would be able to supply all functions necessary to restore a normal cellular phenotype. Complementation is therefore a test of function and enabled the categorization of affected individuals as having the same or different defects. Subsequently, each complementation group was found to result from a defect in a distinct gene [<a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer 2012</a>]. Testing to assign complementation group is not available on a clinical basis, but the complementation group names are used clinically to describe the different phenotypes associated with underlying genes (see <a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object" rid-ob="figobxpTmoleculargenetictestingusedinx">Table 1</a>).</p></div><div id="xp.Prevalence"><h3>Prevalence</h3><p>Prevalence is estimated at 1:1,000,000 in the United States and Europe [<a class="bibr" href="#xp.REF.kleijer.2008.744" rid="xp.REF.kleijer.2008.744">Kleijer et al 2008</a>].</p><p>Certain populations have a higher prevalence. This is usually related to the presence of founder variants (see <a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_notable_patho/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumnotablepatho">Table 9</a>):</p><ul><li class="half_rhythm"><div>In Japan prevalence is estimated at 1:22,000 [<a class="bibr" href="#xp.REF.hirai.2006.171" rid="xp.REF.hirai.2006.171">Hirai et al 2006</a>].</div></li><li class="half_rhythm"><div>In North Africa (Tunisia, Algeria, Morocco, Libya, and Egypt) [<a class="bibr" href="#xp.REF.ben_rekaya.2009.426" rid="xp.REF.ben_rekaya.2009.426">Ben Rekaya et al 2009</a>, <a class="bibr" href="#xp.REF.messaoud.2010.883" rid="xp.REF.messaoud.2010.883">Messaoud et al 2010</a>, <a class="bibr" href="#xp.REF.soufir.2010.1537" rid="xp.REF.soufir.2010.1537">Soufir et al 2010</a>] and the Middle East (Turkey, Israel, and Syria) [<a class="bibr" href="#xp.REF.kraemer.1985.33" rid="xp.REF.kraemer.1985.33">Kraemer & Slor 1985</a>, <a class="bibr" href="#xp.REF.jerbi.2016.439" rid="xp.REF.jerbi.2016.439">Jerbi et al 2016</a>] prevalence is increased, as high as 1:10,000, especially in communities in which consanguinity and endogamy are common [<a class="bibr" href="#xp.REF.sarasin.2019a.e20190046" rid="xp.REF.sarasin.2019a.e20190046">Sarasin et al 2019a</a>].</div></li></ul></div></div><div id="xp.Genetically_Related_Allelic_Disorders"><h2 id="_xp_Genetically_Related_Allelic_Disorders_">Genetically Related (Allelic) Disorders</h2><p>No phenotypes other than those discussed in this <i>GeneReview</i> are known to be associated with germline pathogenic variants in <i>DDB2</i>, <i>POLH</i>, <i>XPA</i>, or <i>XPC</i>.</p><p>In addition to the xeroderma pigmentosum (XP) phenotypes discussed in this <i>GeneReview</i>, pathogenic variants in <i>ERCC1</i>, <i>ERCC2</i>, <i>ERCC3</i>, <i>ERCC4</i>, and <i>ERCC5</i> are known to be associated with cerebrooculofacioskeletal (COFS) syndrome, Fanconi anemia, and trichothiodystrophy (TTD) (<a class="figpopup" href="/books/NBK1397/figure/xp.F1/?report=objectonly" target="object" rid-figpopup="figxpF1" rid-ob="figobxpF1">Figure 1</a>, <a href="/books/NBK1397/table/xp.T.allelic_disorders/?report=objectonly" target="object" rid-ob="figobxpTallelicdisorders">Table 4</a>). (Note: COFS syndrome and TTD should be considered in the differential diagnosis of XP; see <a href="/books/NBK1397/table/xp.T.autosomal_recessive_nucleotide_exci/?report=objectonly" target="object" rid-ob="figobxpTautosomalrecessivenucleotideexci">Table 5</a>.)</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figxpF1" co-legend-rid="figlgndxpF1"><a href="/books/NBK1397/figure/xp.F1/?report=objectonly" target="object" title="Figure 1. " class="img_link icnblk_img figpopup" rid-figpopup="figxpF1" rid-ob="figobxpF1"><img class="small-thumb" src="/books/NBK1397/bin/xp-Image001.gif" src-large="/books/NBK1397/bin/xp-Image001.jpg" alt="Figure 1. " /></a><div class="icnblk_cntnt" id="figlgndxpF1"><h4 id="xp.F1"><a href="/books/NBK1397/figure/xp.F1/?report=objectonly" target="object" rid-ob="figobxpF1">Figure 1. </a></h4><p class="float-caption no_bottom_margin">Relationship between genotype and phenotype in the xeroderma pigmentosum-Cockayne syndrome-trichothiodystrophy spectrum Modified from DiGiovanna & Kraemer [2012]</p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTallelicdisorders"><a href="/books/NBK1397/table/xp.T.allelic_disorders/?report=objectonly" target="object" title="Table 4. " class="img_link icnblk_img" rid-ob="figobxpTallelicdisorders"><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="xp.T.allelic_disorders"><a href="/books/NBK1397/table/xp.T.allelic_disorders/?report=objectonly" target="object" rid-ob="figobxpTallelicdisorders">Table 4. </a></h4><p class="float-caption no_bottom_margin">Allelic Disorders </p></div></div><p>
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<b>Complex phenotypes</b>
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</p><ul><li class="half_rhythm"><div>Allelic complex phenotypes in the differential diagnosis of XP are summarized in <a href="/books/NBK1397/table/xp.T.autosomal_recessive_nucleotide_exci/?report=objectonly" target="object" rid-ob="figobxpTautosomalrecessivenucleotideexci">Table 5</a>.</div></li><li class="half_rhythm"><div>One individual with phenotypic features of Cockayne syndrome, XP, and <a href="/books/n/gene/fa/?report=reader">Fanconi anemia</a> had biallelic pathogenic variants in <i>ERCC4</i> [<a class="bibr" href="#xp.REF.kashiyama.2013.807" rid="xp.REF.kashiyama.2013.807">Kashiyama et al 2013</a>].</div></li><li class="half_rhythm"><div><a class="bibr" href="#xp.REF.niedernhofer.2006.1038" rid="xp.REF.niedernhofer.2006.1038">Niedernhofer et al [2006]</a> described a male age 15 years with biallelic <i>ERCC4</i> pathogenic variants and cachexia, dwarfism, microcephaly, marked sun sensitivity from birth, visual impairment (due to optic atrophy), hearing loss, mild learning disabilities, progressive growth failure, facial features characteristic of premature aging, mild ataxia, and poor coordination. <a class="bibr" href="#xp.REF.niedernhofer.2006.1038" rid="xp.REF.niedernhofer.2006.1038">Niedernhofer et al [2006]</a> proposed that this represented a new progeroid syndrome (see OMIM <a href="https://omim.org/entry/610965" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">610965</a>). Whether XFE progeroid syndrome represents a distinct condition or is part of the spectrum of XP, Fanconi anemia, or XP / Cockayne syndrome has not been determined.</div></li></ul><p><b>Sporadic tumors.</b> Investigation of the association between an increased cancer risk and heterozygosity for an allelic variant causing XP is an active area of research. In addition, sporadic tumors occurring as single tumors in the absence of any other findings of XP may harbor somatic variants in XP-related genes.</p></div><div id="xp.Differential_Diagnosis"><h2 id="_xp_Differential_Diagnosis_">Differential Diagnosis</h2><p>Other nucleotide excision repair disorders associated with cutaneous photosensitivity to consider in the differential diagnosis of xeroderma pigmentosum (XP) are summarized in <a href="/books/NBK1397/table/xp.T.autosomal_recessive_nucleotide_exci/?report=objectonly" target="object" rid-ob="figobxpTautosomalrecessivenucleotideexci">Table 5</a> (see also <a class="figpopup" href="/books/NBK1397/figure/xp.F1/?report=objectonly" target="object" rid-figpopup="figxpF1" rid-ob="figobxpF1">Figure 1</a>) [<a class="bibr" href="#xp.REF.horibata.2004.15410" rid="xp.REF.horibata.2004.15410">Horibata et al 2004</a>, <a class="bibr" href="#xp.REF.berneburg.2007" rid="xp.REF.berneburg.2007">Berneburg & Kraemer 2007</a>, <a class="bibr" href="#xp.REF.kraemer.2007.1388" rid="xp.REF.kraemer.2007.1388">Kraemer et al 2007</a>, <a class="bibr" href="#xp.REF.stefanini.2008" rid="xp.REF.stefanini.2008">Stefanini & Kraemer 2008</a>, <a class="bibr" href="#xp.REF.kraemer.2012" rid="xp.REF.kraemer.2012">Kraemer & Ruenger 2012</a>, <a class="bibr" href="#xp.REF.ruenger.2012" rid="xp.REF.ruenger.2012">Ruenger et al 2012</a>].</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTautosomalrecessivenucleotideexci"><a href="/books/NBK1397/table/xp.T.autosomal_recessive_nucleotide_exci/?report=objectonly" target="object" title="Table 5. " class="img_link icnblk_img" rid-ob="figobxpTautosomalrecessivenucleotideexci"><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="xp.T.autosomal_recessive_nucleotide_exci"><a href="/books/NBK1397/table/xp.T.autosomal_recessive_nucleotide_exci/?report=objectonly" target="object" rid-ob="figobxpTautosomalrecessivenucleotideexci">Table 5. </a></h4><p class="float-caption no_bottom_margin">Autosomal Recessive Nucleotide Excision Repair Disorders Exhibiting Cutaneous Photosensitivity </p></div></div><p><b>Other.</b> In addition to disorders sharing deficient nucleotide excision repair, other conditions exhibiting cutaneous photosensitivity may be considered in the differential diagnosis of XP, especially in individuals with a paucity of other clinical findings. These include the following:</p><ul><li class="half_rhythm"><div><a href="/books/n/gene/rts/?report=reader">Rothmund-Thomson syndrome</a> (RTS). RTS is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma. A variety of benign and malignant hematologic abnormalities have been reported in affected individuals. The rash of RTS typically develops between ages three and six months (occasionally as late as age 2 years) as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. RTS is caused by pathogenic variants in <i>ANAPC1</i> or <i>RECQL4</i> and is inherited in an autosomal recessive manner.</div></li><li class="half_rhythm"><div>Hartnup disorder (OMIM <a href="https://omim.org/entry/234500" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">234500</a>). Affected individuals may have reduced levels of niacin with resulting pellagra-like symptoms of photosensitivity with dermatitis, diarrhea, and dementia. However, individuals with Hartnup disorder are not reported to have increased frequency of skin cancer, as is seen in those with XP. Hartnup disorder is caused by pathogenic variants in <i>SLC6A19</i> and is inherited in an autosomal recessive manner.</div></li><li class="half_rhythm"><div>The cutaneous findings of <a href="/books/n/gene/carney/?report=reader">Carney complex</a> may be confused with those of XP; however, Carney complex is characterized by lentigines without evidence of the usually associated signs of sunlight-induced skin damage such as atrophy and telangiectasia (i.e., poikiloderma), and cutaneous findings are not limited to sun-exposed sites [<a class="bibr" href="#xp.REF.correa.2015.m85" rid="xp.REF.correa.2015.m85">Correa et al 2015</a>].</div></li></ul></div><div id="xp.Management"><h2 id="_xp_Management_">Management</h2><div id="xp.Evaluations_Following_Initial_Diagnos"><h3>Evaluations Following Initial Diagnosis</h3><p>General clinical care guidelines for individuals with xeroderma pigmentosum (XP) have been proposed by the Japanese Dermatological Association [<a class="bibr" href="#xp.REF.moriwaki.2017.1087" rid="xp.REF.moriwaki.2017.1087">Moriwaki et al 2017</a>] (<a href="https://onlinelibrary.wiley.com/doi/epdf/10.1111/1346-8138.13907" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">full text</a>).</p></div><div id="xp.Evaluations_Following_Initial_Diagnos_1"><h3>Evaluations Following Initial Diagnosis</h3><p>To establish the extent of disease and needs in an individual diagnosed with XP, the evaluations summarized in <a href="/books/NBK1397/table/xp.T.recommended_evaluations_following_i/?report=objectonly" target="object" rid-ob="figobxpTrecommendedevaluationsfollowingi">Table 6</a> (if not performed as part of the evaluation that led to the diagnosis) are recommended.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTrecommendedevaluationsfollowingi"><a href="/books/NBK1397/table/xp.T.recommended_evaluations_following_i/?report=objectonly" target="object" title="Table 6. " class="img_link icnblk_img" rid-ob="figobxpTrecommendedevaluationsfollowingi"><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="xp.T.recommended_evaluations_following_i"><a href="/books/NBK1397/table/xp.T.recommended_evaluations_following_i/?report=objectonly" target="object" rid-ob="figobxpTrecommendedevaluationsfollowingi">Table 6. </a></h4><p class="float-caption no_bottom_margin">Recommended Evaluations Following Initial Diagnosis in Individuals with Xeroderma Pigmentosum </p></div></div></div><div id="xp.Treatment_of_Manifestations"><h3>Treatment of Manifestations</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTtreatmentofmanifestationsinindi"><a href="/books/NBK1397/table/xp.T.treatment_of_manifestations_in_indi/?report=objectonly" target="object" title="Table 7. " class="img_link icnblk_img" rid-ob="figobxpTtreatmentofmanifestationsinindi"><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="xp.T.treatment_of_manifestations_in_indi"><a href="/books/NBK1397/table/xp.T.treatment_of_manifestations_in_indi/?report=objectonly" target="object" rid-ob="figobxpTtreatmentofmanifestationsinindi">Table 7. </a></h4><p class="float-caption no_bottom_margin">Treatment of Manifestations in Individuals with Xeroderma Pigmentosum </p></div></div></div><div id="xp.Prevention_of_Primary_Manifestations"><h3>Prevention of Primary Manifestations</h3><p>Treatment of XP depends on early diagnosis and immediate, aggressive avoidance of sun and other UV exposure. This involves avoiding or minimizing outdoor exposure at times when UV radiation is present (when the sun is out or during daytime through clouds).</p><ul><li class="half_rhythm"><div>Clinical suspicion of XP should prompt immediate sun-protective measures until the diagnosis is confirmed or an alternative explanation is determined.</div></li><li class="half_rhythm"><div>Individuals should be educated to protect all body surfaces from UV radiation by wearing protective clothing including hats, long sleeves, long pants and gloves, broad-spectrum, high-SPF sunscreens, UV-absorbing glasses, and long hair styles. Multiple layers of clothing are preferred. The eyes should be protected by wearing UV-absorbing glasses with side shields. Some individuals have custom-made hats with UV-absorbing face shields to permit visibility outdoors while protecting the face from UV.</div></li></ul><p>Because the cells of individuals with XP are hypersensitive to UVA and UVB (found in sunlight) and UVC (found in some artificial light sources), it is useful to measure UV light in an individual's home, school, or work environment with a light meter so that high levels of environmental UV (e.g., halogen lamps) can be identified and eliminated if possible. While no standards exist for perfectly safe UV exposure in individuals with XP, the use of UV meters can alert individuals to unexpected sources of high levels of environmental UV. Unlike UVB, UVA is not blocked by window glass. Windows in areas where individuals with XP will be spending large amounts of time should have UV blocking film applied.</p><p>Low vitamin D levels can result from aggressive avoidance of sun exposure. Vitamin D is produced in the skin by a reaction involving exposure to UV radiation. Active adults with XP and skin cancers received sufficient vitamin D in their diet in the past to result in normal serum concentrations of the active form (1,25 dihydroxy vitamin D) [<a class="bibr" href="#xp.REF.sollitto.1997.942" rid="xp.REF.sollitto.1997.942">Sollitto et al 1997</a>]. However, children protected from sunlight very early in life have had low serum concentration of 25 hydroxy vitamin D; one child became susceptible to bone fractures [<a class="bibr" href="#xp.REF.ali.2009.442" rid="xp.REF.ali.2009.442">Ali et al 2009</a>; Author, personal observation]. Serum vitamin D levels should be monitored and dietary supplementation with oral vitamin D is recommended for persons with low serum concentration of serum vitamin D [<a class="bibr" href="#xp.REF.reichrath.2007.664" rid="xp.REF.reichrath.2007.664">Reichrath 2007</a>; Author, personal communication].</p></div><div id="xp.Surveillance"><h3>Surveillance</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTrecommendedsurveillanceforindivi"><a href="/books/NBK1397/table/xp.T.recommended_surveillance_for_indivi/?report=objectonly" target="object" title="Table 8. " class="img_link icnblk_img" rid-ob="figobxpTrecommendedsurveillanceforindivi"><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="xp.T.recommended_surveillance_for_indivi"><a href="/books/NBK1397/table/xp.T.recommended_surveillance_for_indivi/?report=objectonly" target="object" rid-ob="figobxpTrecommendedsurveillanceforindivi">Table 8. </a></h4><p class="float-caption no_bottom_margin">Recommended Surveillance for Individuals with Xeroderma Pigmentosum </p></div></div></div><div id="xp.AgentsCircumstances_to_Avoid"><h3>Agents/Circumstances to Avoid</h3><p>UV exposure from sunlight and artificial sources of UV radiation should be avoided (see <a href="#xp.Prevention_of_Primary_Manifestations">Prevention of Primary Manifestations</a>).</p><p><b>Artificial sources of UV.</b> Certain light sources (e.g., mercury arc, halogen, and other lamps) can be unrecognized sources of UV. Although such light sources are often shielded, in open areas such as gymnasiums they can be a source of UV if the shield has been breached. UV meters are readily available to enable monitoring of areas to identify unexpected UV sources.</p><p><b>Cigarette smoke.</b> Because cells from individuals with XP are also hypersensitive to environmental mutagens, such as benzo[<i>a</i>]pyrene found in cigarette smoke, prudence dictates that individuals with XP should be protected against these agents. One individual with XP who smoked cigarettes for more than ten years died of bronchogenic carcinoma of the lungs at age 35 years [<a class="bibr" href="#xp.REF.kraemer.1994.1018" rid="xp.REF.kraemer.1994.1018">Kraemer et al 1994</a>]. The authors have cared for another individual with XP who smoked and developed lung cancer in the fifth decade of life.</p></div><div id="xp.Evaluation_of_Relatives_at_Risk"><h3>Evaluation of Relatives at Risk</h3><p>It is appropriate to evaluate the apparently asymptomatic older and younger sibs of an affected individual by molecular genetic testing in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures. Treatment of XP depends on early diagnosis and immediate, aggressive avoidance of sun and other UV exposure (see <a href="#xp.Prevention_of_Primary_Manifestations">Prevention of Primary Manifestations</a>).</p><p>See <a href="#xp.Related_Genetic_Counseling_Issues">Genetic Counseling</a> for issues related to testing of at-risk relatives for genetic counseling purposes.</p></div><div id="xp.Pregnancy_Management"><h3>Pregnancy Management</h3><p>The systemic retinoids isotretinoin and acitretin are used as skin cancer chemopreventive agents in individuals who are actively developing large numbers of skin cancers, and thus may be used by some women with XP [<a class="bibr" href="#xp.REF.kraemer.1988.1633" rid="xp.REF.kraemer.1988.1633">Kraemer et al 1988</a>]. Systemic retinoids are known to be teratogenic to a developing fetus and pose a high risk for birth defects. Therefore, women who are using systemic retinoids should be appropriately counseled about pregnancy risks and the need for effective contraception; regular monitoring with pregnancy tests is indicated. Systemic retinoids should be administered only by physicians who are knowledgeable regarding their risks and benefits.</p><p>To access isotretinoin in the US, women and their prescribing providers must be enrolled in the <a href="https://www.ipledgeprogram.com/default.aspx" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">iPLEDGE program</a> to minimize the potential for fetal exposure. Pregnancy avoidance is initiated before therapy, continues during therapy, and extends post-treatment until the drug is cleared from the body. While both isotretinoin and acitretin may be effective in preventing skin cancers, acitretin may take longer to be eliminated from the body, requiring an extended period (3 years) of post-therapy pregnancy avoidance to minimize teratogenic risk.</p><p>See <a href="https://mothertobaby.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">MotherToBaby</a> for further information on medication use during pregnancy.</p></div><div id="xp.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="xp.Genetic_Counseling"><h2 id="_xp_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="xp.Mode_of_Inheritance"><h3>Mode of Inheritance</h3><p>Xeroderma pigmentosum (XP) is inherited in an autosomal recessive manner.</p></div><div id="xp.Risk_to_Family_Members"><h3>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 individual with XP are presumed to be heterozygous for an XP-related pathogenic variant.</div></li><li class="half_rhythm"><div>If a molecular diagnosis has been established in the proband, molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for an XP-related pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:</div><ul><li class="half_rhythm"><div>One of the pathogenic variants identified in the proband occurred as a <i>de novo</i> event in the proband or as a postzygotic <i>de novo</i> event in a mosaic parent [<a class="bibr" href="#xp.REF.j_nsson.2017.519" rid="xp.REF.j_nsson.2017.519">Jónsson et al 2017</a>].</div></li><li class="half_rhythm"><div>Uniparental isodisomy for the parental chromosome with the pathogenic variant resulted in homozygosity for the pathogenic variant in the proband.</div></li></ul></li><li class="half_rhythm"><div>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</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 an XP-related 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>Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.</div></li></ul><p>
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<b>Offspring of a proband</b>
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</p><ul><li class="half_rhythm"><div>Unless an individual with XP has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for an XP-related pathogenic variant.</div></li><li class="half_rhythm"><div>The offspring of an individual with XP and an individual who is heterozygous for an XP-related pathogenic variant in the same gene as the proband have a 50% chance of having XP. This is a consideration in populations with a founder variant or with a high rate of consanguinity (see <a href="#xp.Prevalence">Prevalence</a> and <a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_notable_patho/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumnotablepatho">Table 9</a>).</div></li></ul><p><b>Other family members.</b> Each sib of the proband's parents is at a 50% risk of being a carrier of an XP-related pathogenic variant.</p></div><div id="xp.Carrier_Detection"><h3>Carrier Detection</h3><p>Carrier testing for at-risk relatives requires prior identification of the XP-related pathogenic variants in the family (see <a class="bibr" href="#xp.REF.christenzaech.2009.1285" rid="xp.REF.christenzaech.2009.1285">Christen-Zaech et al [2009]</a> for discussion).</p></div><div id="xp.Related_Genetic_Counseling_Issues"><h3>Related Genetic Counseling Issues</h3><p>See Management, <a href="#xp.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 and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.</div></li><li class="half_rhythm"><div>It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.</div></li></ul><p><b>DNA banking.</b> Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown).</p></div><div id="xp.Prenatal_Testing_and_Preimplantation"><h3>Prenatal Testing and Preimplantation Genetic Testing</h3><p>Once the XP-related pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for XP are possible.</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="xp.Resources"><h2 id="_xp_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>Action for XP</b>
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</div><div>Westfield, Cushnie, Nr Alford, Aberdeenshire, AB33 8LP</div><div>United Kingdom</div><div><b>Email:</b> support@actionforxp.org</div><div>
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<a href="https://www.actionforxp.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.actionforxp.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Enfants de la Lune</b>
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</div><div>Siège de l’association</div><div>3 Rue Corneille 01200 Bellegarde sur Valserine</div><div>France</div><div><b>Phone:</b> 04 57 05 13 61</div><div><b>Email:</b> contact@enfantsdelalune.org</div><div>
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<a href="https://enfantsdelalune.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.enfantsdelalune.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>Xeroderma Pigmentosum Society, Inc (XP Society)</b>
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</div><div>437 Syndertown Road</div><div>Craryville NY 12521</div><div><b>Phone:</b> 877-XPS-CURE (877-977-2873); 518-851-2612</div><div><b>Email:</b> xps@xps.org</div><div>
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<a href="http://www.xps.org" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.xps.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>XP Family Support Group</b>
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</div><div>10259 Atlantis Drive</div><div>Elk Grove CA 95624</div><div><b>Phone:</b> 916-628-3814</div><div><b>Email:</b> contact@xpfamilysupport.org</div><div>
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<a href="https://xpfamilysupport.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.xpfamilysupport.org</a>
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</div></li><li class="half_rhythm"><div>
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<b>XP Freunde die Mondscheinkinder</b>
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</div><div>Postfach 2124</div><div>48550 Steinfurt</div><div>Germany</div><div><b>Phone:</b> 49 176 200 109 30</div><div><b>Email:</b> info@xerodermapigmentosum.de</div><div>
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<a href="https://www.xerodermapigmentosum.de/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">www.xerodermapigmentosum.de</a>
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</div></li></ul>
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</div><div id="xp.Molecular_Genetics"><h2 id="_xp_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="figxpmolgenTA"><a href="/books/NBK1397/table/xp.molgen.TA/?report=objectonly" target="object" title="Table A." class="img_link icnblk_img" rid-ob="figobxpmolgenTA"><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="xp.molgen.TA"><a href="/books/NBK1397/table/xp.molgen.TA/?report=objectonly" target="object" rid-ob="figobxpmolgenTA">Table A.</a></h4><p class="float-caption no_bottom_margin">Xeroderma Pigmentosum: Genes and Databases </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpmolgenTB"><a href="/books/NBK1397/table/xp.molgen.TB/?report=objectonly" target="object" title="Table B." class="img_link icnblk_img" rid-ob="figobxpmolgenTB"><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="xp.molgen.TB"><a href="/books/NBK1397/table/xp.molgen.TB/?report=objectonly" target="object" rid-ob="figobxpmolgenTB">Table B.</a></h4><p class="float-caption no_bottom_margin">OMIM Entries for Xeroderma Pigmentosum (View All in OMIM) </p></div></div><div id="xp.Molecular_Pathogenesis"><h3>Molecular Pathogenesis</h3><p>An intact DNA repair system that senses, excises, and repairs UV-induced dipyrimidine photoproducts and other forms of DNA damage is necessary to prevent replication errors and subsequent tumorigenesis (<a class="figpopup" href="/books/NBK1397/figure/xp.F2/?report=objectonly" target="object" rid-figpopup="figxpF2" rid-ob="figobxpF2">Figure 2</a>) [<a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer 2012</a>].</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figxpF2" co-legend-rid="figlgndxpF2"><a href="/books/NBK1397/figure/xp.F2/?report=objectonly" target="object" title="Figure 2. " class="img_link icnblk_img figpopup" rid-figpopup="figxpF2" rid-ob="figobxpF2"><img class="small-thumb" src="/books/NBK1397/bin/xp-Image002.gif" src-large="/books/NBK1397/bin/xp-Image002.jpg" alt="Figure 2. " /></a><div class="icnblk_cntnt" id="figlgndxpF2"><h4 id="xp.F2"><a href="/books/NBK1397/figure/xp.F2/?report=objectonly" target="object" rid-ob="figobxpF2">Figure 2. </a></h4><p class="float-caption no_bottom_margin">Nucleotide excision repair (NER) pathway Modified from DiGiovanna & Kraemer [2012]</p></div></div><p>Exposure to UV radiation from sunlight forms cyclobutane dimers or other photoproducts at adjacent pyrimidines, thereby distorting the DNA. Initial lesion recognition in non-transcribed DNA (global genome repair-GGR) is performed by <i>DDB2</i>-encoded protein [<a class="bibr" href="#xp.REF.clement.2010.21" rid="xp.REF.clement.2010.21">Clement et al 2010</a>, <a class="bibr" href="#xp.REF.sugasawa.2010.29" rid="xp.REF.sugasawa.2010.29">Sugasawa 2010</a>]. The <i>XPC</i>-encoded protein binding to the photoproducts is facilitated by the binding of the <i>DDB2</i>-encoded protein. The <i>XPC</i>-encoded protein is complexed with hHR23B and centrin [<a class="bibr" href="#xp.REF.sugasawa.2010.29" rid="xp.REF.sugasawa.2010.29">Sugasawa 2010</a>].</p><p>DNA damage in transcribed genes (transcription coupled repair) is marked by stalled RNA polymerase. The CS (Cockayne syndrome)-encoded proteins (along with others) bind to the damage in the transcribed DNA strand.</p><p>ERCC2 is part of basal transcription factor TFIIH that is involved in regulation of the basal rate of transcription (RNA synthesis) of active genes, as well as in nucleotide excision repair (NER).</p><p>In both global genome repair and transcription-coupled repair, the XPA protein probably functions in conjunction with replication protein A and TFIIH – the basal transcription factor that is involved in regulation of the basal rate of transcription (RNA synthesis) of active genes, as well as in NER. The XPB/ERCC3 and XPD/ERCC2 proteins (helicases that are part of the TFIIH complex) partially unwind the DNA in the region of the damage, thereby exposing the lesion for further processing. The XPF/ERCC4 product, in a complex with ERCC1, makes a single-strand nick at the 5' side of the lesion, while the XPG/ERCC5 product makes a similar nick on the 3' side, resulting in the release of a region of approximately 30 nucleotides containing the damage. The resulting gap is filled by DNA polymerase using the other (undamaged) strand as a template in a process involving proliferating cell nuclear antigen. DNA ligase I seals the region, restoring the original undamaged sequence [<a class="bibr" href="#xp.REF.van_steeg.1999.86" rid="xp.REF.van_steeg.1999.86">van Steeg & Kraemer 1999</a>, <a class="bibr" href="#xp.REF.bootsma.2002" rid="xp.REF.bootsma.2002">Bootsma et al 2002</a>].</p><p>Individuals with the XP variant have a normal nucleotide excision pathway and a defect in <i>POLH</i>, encoding the DNA polymerase eta protein, which can replicate through UV-damaged DNA. Loss of polymerase eta function leads to replication by alternative error-prone polymerases.</p><p><b>Mechanism of disease causation.</b> XP occurs via a loss-of-function mechanism of any of the NER or polymerase eta proteins.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figxpTxerodermapigmentosumnotablepatho"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_notable_patho/?report=objectonly" target="object" title="Table 9. " class="img_link icnblk_img" rid-ob="figobxpTxerodermapigmentosumnotablepatho"><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="xp.T.xeroderma_pigmentosum_notable_patho"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_notable_patho/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumnotablepatho">Table 9. </a></h4><p class="float-caption no_bottom_margin">Xeroderma Pigmentosum: Notable Pathogenic Variants by Gene </p></div></div></div></div><div id="xp.Chapter_Notes"><h2 id="_xp_Chapter_Notes_">Chapter Notes</h2><div id="xp.Author_Notes"><h3>Author Notes</h3><p><b>NIH Study 99-C-0099.</b> Examination of Clinical and Laboratory Abnormalities in Patients with Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy is actively recruiting new patients for a study in Bethesda, MD. Click <a href="https://clinicaltrials.gov/ct2/show/NCT00001813" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">here</a> for more information.</p></div><div id="xp.Acknowledgements"><h3>Acknowledgements</h3><p>This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and National Human Genome Research Institute.</p><p>We wish to thank the many patients and families throughout the world who have participated in the XP protocols at the National Institutes of Health, National Cancer Institute.</p></div><div id="xp.Author_History"><h3>Author History</h3><p>John J DiGiovanna, MD (2011-present)<br />Kenneth H Kraemer, MD (2003-present)<br />Deborah Tamura, RN (2022-present)<br />Daniel J Wattendorf, MD; National Institutes of Health (2003-2008)</p></div><div id="xp.Revision_History"><h3>Revision History</h3><ul><li class="half_rhythm"><div>24 March 2022 (ha) Comprehensive update posted live</div></li><li class="half_rhythm"><div>29 September 2016 (ma) Comprehensive update posted live</div></li><li class="half_rhythm"><div>13 February 2014 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 February 2013 (cd) Revision: changes in testing available for <i>POLH</i>, <i>ERCC3</i>, <i>XPA</i>, <i>XPC</i>, and <i>DDB2</i></div></li><li class="half_rhythm"><div>1 November 2012 (cd) Revision: testing for <i>ERCC4</i> mutations available clinically; <a class="figpopup" href="/books/NBK1397/figure/xp.F2/?report=objectonly" target="object" rid-figpopup="figxpF2" rid-ob="figobxpF2">Figure 2</a> added</div></li><li class="half_rhythm"><div>15 March 2012 (cd) Revision: sequence analysis available clinically for <i>ERCC1</i> and <i>ERCC3</i> and no longer available for <i>DDB2</i></div></li><li class="half_rhythm"><div>4 August 2011 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>22 April 2008 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>14 May 2007 (cd) Revision: sequence analysis clinically available for <i>XPA</i> and <i>XPC</i></div></li><li class="half_rhythm"><div>1 June 2006 (cd) Revision: confirmation of <i>XPA</i> and <i>XPC</i> mutations identified in a research lab clinically available</div></li><li class="half_rhythm"><div>15 September 2005 (me) Comprehensive update posted live</div></li><li class="half_rhythm"><div>24 February 2004 (kk) Revision: Molecular Genetics</div></li><li class="half_rhythm"><div>1 October 2003 (kk) Revision: clinical testing no longer available</div></li><li class="half_rhythm"><div>20 June 2003 (me) Review posted live</div></li><li class="half_rhythm"><div>28 April 2003 (kk) Original submission</div></li></ul><p>Note: Pursuant to 17 USC Section 105 of the United States Copyright Act, the <i>GeneReview</i> "Xeroderma Pigmentosum" is in the public domain in the United States of America.</p></div></div><div id="xp.References"><h2 id="_xp_References_">References</h2><div id="xp.Published_Guidelines__Consensus_State"><h3>Published Guidelines / Consensus Statements</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.moriwaki.2017.1087">Moriwaki S, Kanda F, Hayashi M, Yamashita D, Sakai Y, Nishigori C, et al. Xeroderma pigmentosum clinical practice guidelines. <span><span class="ref-journal">J Dermatol. </span>2017;<span class="ref-vol">44</span>:1087–96.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/28771907" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28771907</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.tamura.2014">Tamura D, Kraemer KH, DiGiovanna JJ. Xeroderma pigmentosum. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. <em>Treatment of Skin Disease: Comprehensive Therapeutic Strategies</em>. 4 ed. London, UK: Elsevier; 2014.</div></p></li></ul></div><div id="xp.Literature_Cited"><h3>Literature Cited</h3><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.ali.2009.442">Ali JT, Mukasa Y, Coulson IH. Xeroderma pigmentosum: early diagnostic features and an adverse consequence of photoprotection. <span><span class="ref-journal">Clin Exp Dermatol. </span>2009;<span class="ref-vol">34</span>:442–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19309384" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19309384</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.arlett.2006.510">Arlett CF, Plowman PN, Rogers PB, Parris CN, Abbaszadeh F, Green MH, McMillan TJ, Bush C, Foray N, Lehmann AR. Clinical and cellular ionizing radiation sensitivity in a patient with xeroderma pigmentosum. <span><span class="ref-journal">Br J Radiol. </span>2006;<span class="ref-vol">79</span>:510–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16714754" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16714754</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.ben_rekaya.2013.316286">Ben Rekaya M, Jerbi M, Messaoud O, Ben Brick AS, Zghal M, Mbarek C, Chadli-Debbiche A, Jones M, Mokni M, Boussen H, Boubaker MS, Fazaa B, Yacoub-Youssef H, Abdelhak S. Further evidence of mutational heterogeneity of the XPC gene in Tunisian families: a spectrum of private and ethnic specific mutations. <span><span class="ref-journal">Biomed Res Int. </span>2013;<span class="ref-vol">2013</span>:316286. </span> [<a href="/pmc/articles/PMC3741899/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3741899</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23984341" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23984341</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.ben_rekaya.2014.256245">Ben Rekaya M, Laroussi N, Messaoud O, Jones M, Jerbi M, Naouali C, Bouyacoub Y, Chargui M, Kefi R, Fazaa B, Boubaker MS, Boussen H, Mokni M, Abdelhak S, Zghal M, Khaled A, Yacoub-Youssef H. A founder large deletion mutation in xeroderma pigmentosum-Variant form in Tunisia: implication for molecular diagnosis and therapy. <span><span class="ref-journal">Biomed Res Int. </span>2014;<span class="ref-vol">2014</span>:256245. </span> [<a href="/pmc/articles/PMC4024419/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4024419</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24877075" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24877075</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.ben_rekaya.2009.426">Ben Rekaya M, Messaoud O, Talmoudi F, Nouira S, Ouragini H, Amouri A, Boussen H, Boubaker S, Mokni M, Mokthar I, Abdelhak S, Zghal M. High frequency of the V548A fs X572 XPC mutation in Tunisia: implication for molecular diagnosis. <span><span class="ref-journal">J Hum Genet. </span>2009;<span class="ref-vol">54</span>:426–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19478817" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19478817</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.berneburg.2007">Berneburg M, Kraemer KH. Xeroderma pigmentosum and other DNA repair-deficient photodermatoses. In: Lim H, Hönigsmann H, Hawk JLM, eds. <em>Photodermatology</em>. New York, NY: Informa Healthcare; 2007:239-50.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.bootsma.2002">Bootsma D, Kraemer KH, Cleaver JE, Hoeijmakers JHJ. Nucleotide excision repair syndromes: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. In: Vogelstein B, Kinzler KW, eds. <em>The Genetic Basis of Human Cancer</em>. 2 ed. New York, NY: McGraw-Hill; 2002:211-37.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.boyle.2008.1194">Boyle J, Ueda T, Oh KS, Imoto K, Tamura D, Jagdeo J, Khan SG, Nadem C, Digiovanna JJ, Kraemer KH. 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Familial predisposition to TP53/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum. <span><span class="ref-journal">Blood. </span>2019b;<span class="ref-vol">133</span>:2718–24.</span> [<a href="/pmc/articles/PMC6610036/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6610036</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30914417" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30914417</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.schwertman.2012.598">Schwertman P, Lagarou A, Dekkers DH, Raams A, van der Hoek AC, Laffeber C, Hoeijmakers JH, Demmers JA, Fousteri M, Vermeulen W, Marteijn JA. UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair. <span><span class="ref-journal">Nat Genet. </span>2012;<span class="ref-vol">44</span>:598–602.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22466611" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22466611</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.sethi.2013.1279">Sethi M, Lehmann AR, Fawcett H, Stefanini M, Jaspers N, Mullard K, Turner S, Robson A, McGibbon D, Sarkany R, Fassihi H. Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions. <span><span class="ref-journal">Br J Dermatol. </span>2013;<span class="ref-vol">169</span>:1279–87.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23889214" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23889214</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.shanbhag.2018.e240">Shanbhag NM, Geschwind MD, DiGiovanna JJ, Groden C, Godfrey R, Yousefzadeh MJ, Wade EA, Niedernhofer LJ, Malicdan MCV, Kraemer KH, Gahl WA, Toro C. Neurodegeneration as the presenting symptom in 2 adults with xeroderma pigmentosum complementation group F. <span><span class="ref-journal">Neurol Genet. </span>2018;<span class="ref-vol">4</span>:e240. </span> [<a href="/pmc/articles/PMC5994703/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5994703</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29892709" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29892709</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.sollitto.1997.942">Sollitto RB, Kraemer KH, DiGiovanna JJ. Normal vitamin D levels can be maintained despite rigorous photoprotection: Six years' experience with xeroderma pigmentosum. <span><span class="ref-journal">J Am Acad Dermatol. </span>1997;<span class="ref-vol">37</span>:942–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/9418761" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9418761</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.soufir.2010.1537">Soufir N, Ged C, Bourillon A, Austerlitz F, Chemin C, Stary A, Armier J, Pham D, Khadir K, Roume J, Hadj-Rabia S, Bouadjar B, Taieb A, de Verneuil H, Benchiki H, Grandchamp B, Sarasin A. A prevalent mutation with founder effect in xeroderma pigmentosum group C from north Africa. <span><span class="ref-journal">J Invest Dermatol. </span>2010;<span class="ref-vol">130</span>:1537–42.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20054342" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20054342</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.stefanini.2008">Stefanini M, Kraemer KHK. Xeroderma pigmentosum. In: Ruggieri M, Pascual-Castroviejo I, Di Rocco C, eds. <em>Neurocutaneous Diseases</em>. New York, NY: Springer; 2008:771-92.</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.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="xp.REF.sugasawa.2010.29">Sugasawa K. Regulation of damage recognition in mammalian global genomic nucleotide excision repair. <span><span class="ref-journal">Mutat Res. </span>2010;<span class="ref-vol">685</span>:29–37.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19682467" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19682467</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.tamhankar.2015.16">Tamhankar PM, Iyer SV, Ravindran S, Gupta N, Kabra M, Nayak C, Kura M, Sanghavi S, Joshi R, Chennuri VS, Khopkar U. Clinical profile and mutation analysis of xeroderma pigmentosum in Indian patients. <span><span class="ref-journal">Indian J Dermatol Venereol Leprol. </span>2015;<span class="ref-vol">81</span>:16–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25566891" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25566891</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.tamura.2012.1308">Tamura D, Khan SG, Merideth M, DiGiovanna JJ, Tucker MA, Goldstein AM, Oh K-S, Ueda T, Boyle J, Sarihan M, Kraemer KH. Effect of mutations in XPD (ERCC2) on pregnancy and prenatal development in mothers of patients with trichothiodystrophy or xeroderma pigmentosum. <span><span class="ref-journal">Eur J Hum Genet. </span>2012;<span class="ref-vol">20</span>:1308–10.</span> [<a href="/pmc/articles/PMC3499748/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3499748</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22617342" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22617342</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.tamura.2011.1046">Tamura D, Merideth M, DiGiovanna JJ, Zhou X, Tucker MA, Goldstein AM, Brooks BP, Khan SG, Oh KS, Ueda T, Boyle J, Moslehi R, Kraemer KH. High-risk pregnancy and neonatal complications in the DNA repair and transcription disorder trichothiodystrophy: report of 27 affected pregnancies. <span><span class="ref-journal">Prenat Diagn. </span>2011;<span class="ref-vol">31</span>:1046–53.</span> [<a href="/pmc/articles/PMC3266696/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3266696</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21800331" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21800331</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.van_steeg.1999.86">van Steeg H, Kraemer KH. Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer. <span><span class="ref-journal">Mol Med Today. </span>1999;<span class="ref-vol">5</span>:86–94.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10200950" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10200950</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.wilson.2016.773">Wilson BT, Lochan A, Stark Z, Sutton RE. Novel missense mutations in a conserved loop between ERCC6 (CSB) helicase motifs V and VI: Insights into Cockayne syndrome. <span><span class="ref-journal">Am J Med Genet A. </span>2016;<span class="ref-vol">170</span>:773–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/26749132" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26749132</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="xp.REF.zhang.2012.593">Zhang X, Horibata K, Saijo M, Ishigami C, Ukai A, Kanno S, Tahara H, Neilan EG, Honma M, Nohmi T, Yasui A, Tanaka K. Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair. <span><span class="ref-journal">Nat Genet. </span>2012;<span class="ref-vol">44</span>:593–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22466612" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22466612</span></a>]</div></p></li></ul></div></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK1397_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><div class="contrib half_rhythm"><span itemprop="author">Kenneth H Kraemer</span>, MD<div class="affiliation small">Laboratory of Cancer Biology and Genetics
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Center for Cancer Research
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National Cancer Institute
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Bethesda, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin@kremeark" class="oemail">vog.hin@kremeark</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">John J DiGiovanna</span>, MD<div class="affiliation small">Laboratory of Cancer Biology and Genetics
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Center for Cancer Research
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National Cancer Institute
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Bethesda, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.liam@avoigidj" class="oemail">vog.hin.liam@avoigidj</a></div></div></div><div class="contrib half_rhythm"><span itemprop="author">Deborah Tamura</span>, RN<div class="affiliation small">Laboratory of Cancer Biology and Genetics
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Center for Cancer Research
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National Cancer Institute
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Bethesda, Maryland<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.liam@darumat" class="oemail">vog.hin.liam@darumat</a></div></div></div><h3>Publication History</h3><p class="small">Initial Posting: <span itemprop="datePublished">June 20, 2003</span>; Last Update: <span itemprop="dateModified">March 24, 2022</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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a registered trademark of the University of Washington, Seattle. All rights
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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>Kraemer KH, DiGiovanna JJ, Tamura D. Xeroderma Pigmentosum. 2003 Jun 20 [Updated 2022 Mar 24]. 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/sedt/?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/xia-gibbs/?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="figobxpTmoleculargenetictestingusedinx"><div id="xp.T.molecular_genetic_testing_used_in_x" class="table"><h3><span class="label">Table 1. </span></h3><div class="caption"><p>Molecular Genetic Testing Used in Xeroderma Pigmentosum</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.molecular_genetic_testing_used_in_x_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" style="text-align:left;vertical-align:middle;">Gene <sup>1, 2</sup></th><th id="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" style="text-align:left;vertical-align:middle;">Familiar Clinical Disease (Complementation Group) Name</th><th id="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="2" scope="col" colspan="1" headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" style="text-align:left;vertical-align:middle;">Proportion of XP Attributed to Pathogenic Variants in Gene <sup>3</sup></th><th id="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Proportion of Pathogenic Variants <sup>4</sup> Detectable by Method</th></tr><tr><th headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4" id="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:middle;">Sequence analysis <sup>5</sup></th><th headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4" id="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene-targeted deletion/duplication analysis <sup>6</sup></th></tr></thead><tbody><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DDB2</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-E</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">19/19 <sup>7</sup></td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_2" rowspan="4" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>8</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC1</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">ERCC1</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><0.5%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2/2 <sup>7, 9</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC2</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-D</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>99% <sup>7</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC3</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-B</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">0.5%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">8/8 <sup>7, 10</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC4</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-F</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">2%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>99% <sup>7</sup></td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Rare</td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC5</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-G</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">1%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">>99% <sup>7</sup></td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>8</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>POLH</i>
|
|
</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP VARIANT (XP-V)</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">23.5%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">85% <sup>7, 11</sup></td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">15% <sup>7, 11</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<i>XPA</i>
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|
</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-A</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">30%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>7</sup></td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_2" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Unknown <sup>8</sup></td></tr><tr><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>XPC</i>
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</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP-C</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">27%</td><td headers="hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_1_4 hd_h_xp.T.molecular_genetic_testing_used_in_x_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100% <sup>7</sup></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">XP = xeroderma pigmentosum</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="xp.TF.1.1"><p class="no_margin">Genes are listed in alphabetic order.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="xp.TF.1.2"><p class="no_margin">See <a href="/books/NBK1397/?report=reader#xp.molgen.TA">Table A. Genes and Databases</a> for chromosome locus and protein.</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="xp.TF.1.3"><p class="no_margin"><a class="bibr" href="#xp.REF.martens.2021.1173" rid="xp.REF.martens.2021.1173">Martens et al [2021]</a>; Authors, personal observation</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="xp.TF.1.4"><p class="no_margin">See <a href="#xp.Molecular_Genetics">Molecular Genetics</a> for information on variants detected in these genes.</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="xp.TF.1.5"><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>6. </dt><dd><div id="xp.TF.1.6"><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>7. </dt><dd><div id="xp.TF.1.7"><p class="no_margin">Data derived from the subscription-based professional view of Human Gene Mutation Database [<a class="bibr" href="#xp.REF.stenson.2020.1197" rid="xp.REF.stenson.2020.1197">Stenson et al 2020</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="xp.TF.1.8"><p class="no_margin">No data on detection rate of gene-targeted deletion/duplication analysis are available.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="xp.TF.1.9"><p class="no_margin"><a class="bibr" href="#xp.REF.jaspers.2007.457" rid="xp.REF.jaspers.2007.457">Jaspers et al [2007]</a>; <a class="bibr" href="#xp.REF.kashiyama.2013.807" rid="xp.REF.kashiyama.2013.807">Kashiyama et al [2013]</a>; Authors, personal observation</p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="xp.TF.1.10"><p class="no_margin"><a class="bibr" href="#xp.REF.oh.2006.1092" rid="xp.REF.oh.2006.1092">Oh et al [2006]</a>, <a class="bibr" href="#xp.REF.fassihi.2016.e1236" rid="xp.REF.fassihi.2016.e1236">Fassihi et al [2016]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>11. </dt><dd><div id="xp.TF.1.11"><p class="no_margin">
|
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<a class="bibr" href="#xp.REF.opletalova.2014.117" rid="xp.REF.opletalova.2014.117">Opletalova et al [2014]</a>
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|
</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTxerodermapigmentosumfrequencyof"><div id="xp.T.xeroderma_pigmentosum_frequency_of" class="table"><h3><span class="label">Table 2. </span></h3><div class="caption"><p>Xeroderma Pigmentosum: Frequency of Select Features</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_frequency_of/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.xeroderma_pigmentosum_frequency_of_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Feature</th><th id="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">% of Persons w/Feature</th><th id="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Acute sunburn reaction w/minimal UV exposure</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">60%</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Freckle-like lesions on sun-exposed skin</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Xerosis & poikiloderma on sun-exposed skin</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">100%</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Extent of xerosis & poikiloderma is dependent on amount of sun/UV exposure.</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Ocular abnormalities</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">90%</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Limited to anterior, UV-exposed portion of eyes & lids</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurologic abnormalities</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">25%</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Primarily in those w/pathogenic variants in <i>ERCC2</i>, <i>ERCC3</i>, <i>ERCC4</i>, <i>ERCC5</i>, or <i>XPA</i></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cutaneous neoplasia</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">65%</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency & extent of neoplastic lesions is dependent on amount of sun/UV exposure.</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Other neoplasias</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">10- to 20-fold increase</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_frequency_of_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Internal neoplasms incl brain & CNS tumors, hematologic malignancies, breast cancer, tumors of female reproductive tract, papillary thyroid cancer, kidney cancer, & cancer in smokers have been reported.</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">CNS = central nervous system</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTxerodermapigmentosumphenotypecor"><div id="xp.T.xeroderma_pigmentosum_phenotype_cor" class="table"><h3><span class="label">Table 3. </span></h3><div class="caption"><p>Xeroderma Pigmentosum: Phenotype Correlations by Gene</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_phenotype_cor/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.xeroderma_pigmentosum_phenotype_cor_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene</th><th id="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP w/o Neurologic Abnormalities</th><th id="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP w/Mild Neurologic Abnormalities</th><th id="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP w/Severe Neurologic Abnormalities</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>DDB2</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC1</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>ERCC2</i>
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|
</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC3</i>
|
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC4</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">● <sup>1</sup></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC5</i>
|
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>POLH</i>
|
|
</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>XPA</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>XPC</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">●</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_phenotype_cor_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="xp.TF.3.1"><p class="no_margin">When present in those with <i>ERCC4</i> pathogenic variants, the neurologic abnormalities are of late onset.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTallelicdisorders"><div id="xp.T.allelic_disorders" class="table"><h3><span class="label">Table 4. </span></h3><div class="caption"><p>Allelic Disorders</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.allelic_disorders/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.allelic_disorders_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.allelic_disorders_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_xp.T.allelic_disorders_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Allelic Disorder</th><th id="hd_h_xp.T.allelic_disorders_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Characteristics</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC1</i>
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<br />
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<i>ERCC2</i>
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<br />
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<i>ERCC5</i>
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</td><td headers="hd_h_xp.T.allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cerebrooculofacioskeletal syndrome <sup>1</sup> (OMIM <a href="https://omim.org/phenotypicSeries/PS214150" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS214150</a>)</td><td headers="hd_h_xp.T.allelic_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#xp.Differential_Diagnosis">Differential Diagnosis</a>.</td></tr><tr><td headers="hd_h_xp.T.allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC2</i>
|
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<br />
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<i>ERCC3</i>
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</td><td headers="hd_h_xp.T.allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Trichothiodystrophy <sup>1</sup> (OMIM <a href="https://omim.org/phenotypicSeries/PS601675" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS601675</a>)</td><td headers="hd_h_xp.T.allelic_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See <a href="#xp.Differential_Diagnosis">Differential Diagnosis</a>.</td></tr><tr><td headers="hd_h_xp.T.allelic_disorders_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC4</i>
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</td><td headers="hd_h_xp.T.allelic_disorders_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="/books/n/gene/fa/?report=reader">Fanconi anemia</a>
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</td><td headers="hd_h_xp.T.allelic_disorders_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Heterogeneous condition characterized by physical abnormalities, bone marrow failure, & ↑ risk for malignancy</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="xp.TF.4.1"><p class="no_margin">See <a href="#xp.Differential_Diagnosis">Differential Diagnosis</a> for other genes associated with this phenotype.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTautosomalrecessivenucleotideexci"><div id="xp.T.autosomal_recessive_nucleotide_exci" class="table"><h3><span class="label">Table 5. </span></h3><div class="caption"><p>Autosomal Recessive Nucleotide Excision Repair Disorders Exhibiting Cutaneous Photosensitivity</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.autosomal_recessive_nucleotide_exci/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.autosomal_recessive_nucleotide_exci_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Gene(s)</th><th id="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Disorder <sup>1</sup></th><th id="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Clinical Features / Comment</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ERCC1</i> <sup>1</sup><br /><i>ERCC2</i> <sup>1</sup><br /><i>ERCC5</i> <sup>1</sup><br /><i>ERCC6</i> <sup>2</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Cerebrooculofacioskeletal syndrome (COFS; OMIM <a href="https://omim.org/phenotypicSeries/PS214150" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS214150</a>)</td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Progressive neurologic disorder marked by microcephaly w/intracranial calcifications, growth failure, ocular findings (microcornea, cataracts, optic atrophy) & congenital joint contractures. Photosensitivity may occur w/concurrent cellular phenotype of UV sensitivity.</td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ERCC2</i> <sup>1</sup><br /><i>ERCC3</i> <sup>1</sup><br /><i>GTF2H5</i><br /><i>GTF2E2</i> <sup>3</sup><br /><i>MPLKIP</i> <sup>4</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Trichothiodystrophy (TTD; OMIM <a href="https://omim.org/phenotypicSeries/PS601675" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PS601675</a>)</td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Variable phenotype incl photosensitivity, ichthyosis, brittle hair w/"tiger tail" appearance under polarizing microscopy, intellectual impairment, short stature, microcephaly, dysmyelination of brain, & characteristic facial features of protruding ears & micrognathia. 20-fold ↑ risk of death before age 10 yrs, primarily from infections. Frequency of pregnancy complications & neonatal abnormalities is ↑ in <i>ERCC2-</i>related TTD but not in mothers w/XP w/different pathogenic variants in <i>ERCC2.</i> <sup>5</sup></td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ERCC2</i> <sup>1</sup><br /><i>ERCC3</i> <sup>1</sup><br /><i>ERCC4</i> <sup>1</sup><br /><i>ERCC5</i> <sup>1, 6, 7</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">XP / Cockayne syndrome (CS) complex</td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assoc w/facial freckling & early skin cancers typical of XP & some features of CS (e.g., ID, spasticity, short stature, hypogonadism) but not skeletal dysplasia. Unlike XP, in which neuronal degeneration predominates, retinal pigmentary changes, calcification of basal ganglia, & dysmyelination typical of CS are observed in XP/CS.</td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><i>ERCC2</i> <sup>1</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">COFS/TTD <sup>8</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Combined features of COFS & TTD. Hair may be short, brittle, & will demonstrate "tiger tail" banding under polarizing microscopy.</td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">CS/TTD complex <sup>8</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Combined features of CS & TTD. Hair may be short, brittle, & will demonstrate "tiger tail" banding under polarizing microscopy.</td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">XP/TTD complex <sup>9</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Phenotypic features of TTD w/clinical & cellular phenotype of XP. Unlike most people w/TTD, those w/XP/TTD may experience ↑ frequency of skin cancers.</td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>ERCC6</i>
|
|
<br />
|
|
<i>ERCC8</i>
|
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</td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="/books/n/gene/cockayne/?report=reader">Cockayne syndrome</a>
|
|
</td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">CS type I (classic form): normal prenatal growth w/onset of growth & developmental abnormalities in 1st 2 yrs. When disease fully manifests, height, weight, & head circumference are far below 5th %ile. Progressive impairment of vision, hearing & CNS/PNS function → severe disability. Death typically in 1<sup>st</sup>-2nd decade. As in XP, cells from those w/CS are hypersensitive to killing by UV, but CS cells have normal post-UV UDS. CS cells also have delayed recovery of RNA synthesis after UV exposure, reflecting their deficiency in transcription-coupled NER.</td></tr><tr><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><i>ERCC6</i> <sup>10</sup><br /><i>ERCC8</i> <sup>10</sup><br /><i>UVSSA</i> <sup>10</sup></td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">UV-sensitive syndrome</td><td headers="hd_h_xp.T.autosomal_recessive_nucleotide_exci_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Mild photosensitivity w/o pigmentary abnormalities or apparent defects in CNS. Cells from affected persons have same transcription defects as those in persons w/CS.</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">COFS = cerebrooculofacioskeletal syndrome; CNS = central nervous system; CS = Cockayne syndrome; ID = intellectual disability; NER = nucleotide excision repair; PNS = peripheral nervous system; TTD = trichothiodystrophy; UDS = unscheduled DNA synthesis; XP = xeroderma pigmentosum</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="xp.TF.5.1"><p class="no_margin">Allelic with XP</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="xp.TF.5.2"><p class="no_margin"><a class="bibr" href="#xp.REF.meira.2000.1221" rid="xp.REF.meira.2000.1221">Meira et al [2000]</a>, <a class="bibr" href="#xp.REF.graham.2001.291" rid="xp.REF.graham.2001.291">Graham et al [2001]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="xp.TF.5.3"><p class="no_margin">
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<a class="bibr" href="#xp.REF.kuschal.2016.627" rid="xp.REF.kuschal.2016.627">Kuschal et al [2016]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="xp.TF.5.4"><p class="no_margin"><a class="bibr" href="#xp.REF.broughton.2001.2539" rid="xp.REF.broughton.2001.2539">Broughton et al [2001]</a>, <a class="bibr" href="#xp.REF.itin.2001.891" rid="xp.REF.itin.2001.891">Itin et al [2001]</a>, <a class="bibr" href="#xp.REF.bootsma.2002" rid="xp.REF.bootsma.2002">Bootsma et al [2002]</a>, <a class="bibr" href="#xp.REF.gigliamari.2004.714" rid="xp.REF.gigliamari.2004.714">Giglia-Mari et al [2004]</a>, <a class="bibr" href="#xp.REF.liang.2005.224" rid="xp.REF.liang.2005.224">Liang et al [2005]</a>, <a class="bibr" href="#xp.REF.kraemer.2007.1388" rid="xp.REF.kraemer.2007.1388">Kraemer et al [2007]</a>, <a class="bibr" href="#xp.REF.heller.2015.734" rid="xp.REF.heller.2015.734">Heller et al [2015]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="xp.TF.5.5"><p class="no_margin"><a class="bibr" href="#xp.REF.moslehi.2010.365" rid="xp.REF.moslehi.2010.365">Moslehi et al [2010]</a>, <a class="bibr" href="#xp.REF.tamura.2011.1046" rid="xp.REF.tamura.2011.1046">Tamura et al [2011]</a>, <a class="bibr" href="#xp.REF.tamura.2012.1308" rid="xp.REF.tamura.2012.1308">Tamura et al [2012]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>6. </dt><dd><div id="xp.TF.5.6"><p class="no_margin">See <a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_phenotype_cor/?report=objectonly" target="object" rid-ob="figobxpTxerodermapigmentosumphenotypecor">Table 3</a> and <a class="figpopup" href="/books/NBK1397/figure/xp.F1/?report=objectonly" target="object" rid-figpopup="figxpF1" rid-ob="figobxpF1">Figure 1</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>7. </dt><dd><div id="xp.TF.5.7"><p class="no_margin">
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<a class="bibr" href="#xp.REF.kashiyama.2013.807" rid="xp.REF.kashiyama.2013.807">Kashiyama et al [2013]</a>
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</p></div></dd></dl><dl class="bkr_refwrap"><dt>8. </dt><dd><div id="xp.TF.5.8"><p class="no_margin">See <a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer [2012]</a>.</p></div></dd></dl><dl class="bkr_refwrap"><dt>9. </dt><dd><div id="xp.TF.5.9"><p class="no_margin"><a class="bibr" href="#xp.REF.broughton.2001.2539" rid="xp.REF.broughton.2001.2539">Broughton et al [2001]</a>, <a class="bibr" href="#xp.REF.boyle.2008.1194" rid="xp.REF.boyle.2008.1194">Boyle et al [2008]</a>, <a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer [2012]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>10. </dt><dd><div id="xp.TF.5.10"><p class="no_margin"><a class="bibr" href="#xp.REF.itoh.1994.233" rid="xp.REF.itoh.1994.233">Itoh et al [1994]</a>, <a class="bibr" href="#xp.REF.horibata.2004.15410" rid="xp.REF.horibata.2004.15410">Horibata et al [2004]</a>, <a class="bibr" href="#xp.REF.nardo.2009.6209" rid="xp.REF.nardo.2009.6209">Nardo et al [2009]</a>, <a class="bibr" href="#xp.REF.nakazawa.2012.586" rid="xp.REF.nakazawa.2012.586">Nakazawa et al [2012]</a>, <a class="bibr" href="#xp.REF.schwertman.2012.598" rid="xp.REF.schwertman.2012.598">Schwertman et al [2012]</a>, <a class="bibr" href="#xp.REF.zhang.2012.593" rid="xp.REF.zhang.2012.593">Zhang et al [2012]</a>, <a class="bibr" href="#xp.REF.wilson.2016.773" rid="xp.REF.wilson.2016.773">Wilson et al [2016]</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTrecommendedevaluationsfollowingi"><div id="xp.T.recommended_evaluations_following_i" class="table"><h3><span class="label">Table 6. </span></h3><div class="caption"><p>Recommended Evaluations Following Initial Diagnosis in Individuals with Xeroderma Pigmentosum</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.recommended_evaluations_following_i/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.recommended_evaluations_following_i_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" rowspan="4" scope="row" colspan="1" style="text-align:left;vertical-align:middle;"><b>Photosensitivity</b><br />& <b>accelerated</b><br /><b>photoaging</b></td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Baseline exam of skin (incl all sun-exposed as well as sun-shielded areas)</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="2" colspan="1" style="text-align:left;vertical-align:middle;">Look for evidence of sunlight-induced damage incl pigmentary changes, precancerous lesions, & skin cancers.</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" colspan="1" scope="col" rowspan="1" style="text-align:left;vertical-align:middle;">Examine scalp using hair dryer (on a cool setting) to blow hair aside.</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Exam of lip & adjacent tip of tongue</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Check for signs of sun damage, incl actinic cheilitis (type of actinic keratosis or leukoplakia occurring on lips) & prominent telangiectasia, which may precede development of cancer in these areas.</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Baseline clinical color photographs of entire skin surface w/close-ups (incl ruler) of individual lesions</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To facilitate follow up & detection of early skin cancers</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Sun-induced</b>
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<br />
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<b>damage to eyes</b>
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<br />
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<b>& degenerative</b>
|
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<br />
|
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<b>changes to lens</b>
|
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<br />
|
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<b>(cataract) & retina</b>
|
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</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Examine lids & anterior UV-exposed portions of globe as well as retina.</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Look for evidence of sun-induced damage incl ectropion, entropion, inflammatory masses (pterygia, pinguecula), clouding of cornea, cataracts, & cancer of lids, conjunctiva, or cornea.</div></li><li class="half_rhythm"><div>Eversion of lids may be necessary to detect cancers of mucosal surface.</div></li><li class="half_rhythm"><div>Dilated eye exam looking for retinal changes</div></li></ul>
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</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Schirmer test to detect dry eyes</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">This test involves measurement of extent of absorption of tears into filter paper placed under eyelids for a few minutes.</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<b>Progressive</b>
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<br />
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<b>neurologic</b>
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<br />
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<b>abnormalities</b>
|
|
</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Baseline developmental assessment in children & assess for need for educational support.</div></li><li class="half_rhythm"><div>Neurologic eval w/baseline neurocognitive testing if neurologic problems are detected</div></li><li class="half_rhythm"><div>Measurement of head circumference to determine if microcephaly is present.</div></li><li class="half_rhythm"><div>Deep tendon reflex testing</div></li><li class="half_rhythm"><div>MRI of brain & NCVs, if other neurologic problems are detected</div></li><li class="half_rhythm"><div>Baseline audiometry eval to screen for sensorineural hearing loss</div></li></ul>
|
|
</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Thyroid</b>
|
|
<br />
|
|
<b>abnormalities</b>
|
|
</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Palpation of thyroid &/or thyroid ultrasound assessing for presence of thyroid nodules</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Thyroid ultrasound is more sensitive in identifying presence of thyroid nodules.</div></li><li class="half_rhythm"><div>TI-RADS score provides descriptors for suspicion levels of nodules.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Genetic</b>
|
|
<br />
|
|
<b>counseling</b>
|
|
</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">By genetics professionals <sup>1</sup></td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">To inform affected persons & families re nature, MOI, & implications of XP to facilitate medical & personal decision making</td></tr><tr><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Family support</b>
|
|
<br />
|
|
<b>& resources</b>
|
|
</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Assess need for:
|
|
<ul><li class="half_rhythm"><div>Community or <a href="#xp.Resources">online resources</a> incl XP support groups;</div></li><li class="half_rhythm"><div>Social work involvement for parental support;</div></li><li class="half_rhythm"><div>Home nursing referral.</div></li></ul>
|
|
</td><td headers="hd_h_xp.T.recommended_evaluations_following_i_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">MOI = mode of inheritance; NCV = nerve conduction velocity; XP = xeroderma pigmentosum</p></div></dd></dl><dl class="bkr_refwrap"><dt>1. </dt><dd><div id="xp.TF.6.1"><p class="no_margin">Medical geneticist, certified genetic counselor, certified advanced genetic nurse</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTtreatmentofmanifestationsinindi"><div id="xp.T.treatment_of_manifestations_in_indi" class="table"><h3><span class="label">Table 7. </span></h3><div class="caption"><p>Treatment of Manifestations in Individuals with Xeroderma Pigmentosum</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.treatment_of_manifestations_in_indi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.treatment_of_manifestations_in_indi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Manifestation/Concern</th><th id="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment</th><th id="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Considerations/Other</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Premalignant lesions</b>
|
|
<br />
|
|
<b>(e.g., actinic keratoses)</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Freezing w/liquid nitrogen</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Larger areas of sun-</b>
|
|
<br />
|
|
<b>damaged skin</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Field treatments such as topical 5-fluorouracil or imiquimod preparations <sup>1</sup></td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Rarely, therapeutic dermatome shaving or dermabrasion is used to remove more damaged superficial epidermal layers.</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">This procedure permits repopulation by relatively UV-shielded cells from follicles & glands.</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Cutaneous neoplasms</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Treatment as in persons w/o XP</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Involves electrodesiccation/curettage, surgical excision, or Mohs micrographic surgery</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Recurrent skin cancers</b>
|
|
<br />
|
|
<b>(or skin cancers in</b>
|
|
<br />
|
|
<b>locations at high risk</b>
|
|
<br />
|
|
<b>for recurrence)</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Best treated w/Mohs micrographic surgery</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Because multiple surgical procedures are often needed, removal of non-cancerous skin should be minimized.</div></li><li class="half_rhythm"><div>Severe cases have been treated by excision of large portions of facial surface & grafting w/sun-protected skin.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Active development</b>
|
|
<br />
|
|
<b>of large numbers of</b>
|
|
<br />
|
|
<b>new tumors</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Oral isotretinoin or acitretin can be effective in preventing new neoplasms in persons w/multiple skin cancers after removal of existing cancers. <sup>2</sup></td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Some persons may respond to lower doses of isotretinoin or acitretin w/less toxicity.</div></li><li class="half_rhythm"><div>Toxicity incl hepatic, hyperlipidemic, & teratogenic effects; calcification of ligaments & tendons; premature closure of epiphyses.</div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Metastatic melanoma</b>
|
|
<br />
|
|
<b>& invasive squamous</b>
|
|
<br />
|
|
<b>cell carcinoma</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Systemic chemotherapy w/anti-PD1, anti-PDL-1, & BRAF inhibitors <sup>3</sup></td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Monitor for systemic autoimmune adverse events.</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hematologic</b>
|
|
<br />
|
|
<b>malignancies</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Standard chemotherapy</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Bone marrow transplant has not been successful in XP.</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Internal malignancies</b>
|
|
<br />
|
|
<b>(e.g., brain, lung)</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Standard therapy</div></li><li class="half_rhythm"><div>When x-radiation therapy is indicated, an initial small dose is advisable to test for clinical hypersensitivity.</div></li></ul>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Most persons w/XP are not abnormally sensitive to therapeutic x-rays & have responded normally to full-dose therapeutic x-radiation for treatment of inoperable neoplasms. <sup>4</sup></div></li><li class="half_rhythm"><div>However, cultured cells from a few persons w/XP were found to be hypersensitive to x-radiation. <sup>5</sup></div></li></ul>
|
|
</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Thyroid nodules</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Biopsy of suspicious nodules</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Thyroidectomy if cancer is identified</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neoplasms of eyelids,</b>
|
|
<br />
|
|
<b>conjunctiva, & cornea</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Surgical treatment</div></li><li class="half_rhythm"><div>Topical 5-fluorouracil 1%</div></li><li class="half_rhythm"><div>Topical interferon beta 1b</div></li></ul>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Corneal injury assoc</b>
|
|
<br />
|
|
<b>w/eyelid abnormality</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Methylcellulose eye drops or soft contact lenses to keep cornea moist & protect against mechanical trauma</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"></td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Severe keratitis</b>
|
|
<br />
|
|
<b>w/corneal opacity</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Corneal transplantation</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Immunosuppression necessary to prevent transplant rejection may ↑ risk for skin cancer.</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing loss</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;"><ul><li class="half_rhythm"><div>Use of hearing aids</div></li><li class="half_rhythm"><div>Cochlear implants</div></li></ul>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">See also <a href="/books/n/gene/deafness-overview/?report=reader">Deafness and Hereditary Hearing Loss Overview</a>.</td></tr><tr><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Premature</b>
|
|
<br />
|
|
<b>menopause</b>
|
|
</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Hormone replacement therapy</td><td headers="hd_h_xp.T.treatment_of_manifestations_in_indi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Persons w/XP may be at ↑ risk for osteoporosis & cardiovascular disease due to premature menopause.</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="xp.TF.7.1"><p class="no_margin">
|
|
<a class="bibr" href="#xp.REF.lambert.2015.475" rid="xp.REF.lambert.2015.475">Lambert & Lambert [2015]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="xp.TF.7.2"><p class="no_margin">
|
|
<a class="bibr" href="#xp.REF.kraemer.1988.1633" rid="xp.REF.kraemer.1988.1633">Kraemer et al [1988]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="xp.TF.7.3"><p class="no_margin"><a class="bibr" href="#xp.REF.chambon.2018.65" rid="xp.REF.chambon.2018.65">Chambon et al [2018]</a>, <a class="bibr" href="#xp.REF.salomon.2018.1199" rid="xp.REF.salomon.2018.1199">Salomon et al [2018]</a></p></div></dd></dl><dl class="bkr_refwrap"><dt>4. </dt><dd><div id="xp.TF.7.4"><p class="no_margin">
|
|
<a class="bibr" href="#xp.REF.digiovanna.1998.153" rid="xp.REF.digiovanna.1998.153">DiGiovanna et al [1998]</a>
|
|
</p></div></dd></dl><dl class="bkr_refwrap"><dt>5. </dt><dd><div id="xp.TF.7.5"><p class="no_margin">
|
|
<a class="bibr" href="#xp.REF.arlett.2006.510" rid="xp.REF.arlett.2006.510">Arlett et al [2006]</a>
|
|
</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpTrecommendedsurveillanceforindivi"><div id="xp.T.recommended_surveillance_for_indivi" class="table"><h3><span class="label">Table 8. </span></h3><div class="caption"><p>Recommended Surveillance for Individuals with Xeroderma Pigmentosum</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.recommended_surveillance_for_indivi/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.recommended_surveillance_for_indivi_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_1" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">System/Concern</th><th id="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Evaluation</th><th id="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Frequency</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_1" rowspan="2" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Skin</b>
|
|
</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam by physician</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 3-12 mos depending on severity of skin disease</td></tr><tr><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">Exam by affected person or caregivers to look for abnormal pigmented lesions or appearance of basal cell or squamous cell carcinoma (requires instruction in recognition of cutaneous neoplasms)</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Whenever caregivers have opportunity to view affected child’s skin; at least 1x/wk</td></tr><tr><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Eyes</b>
|
|
</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Exam for signs of UV exposure & damage</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">At least every 6 mos depending on severity of ocular UV exposure & damage</td></tr><tr><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Neurologic</b>
|
|
</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Routine neurologic exam for progressive neurologic abnormalities that are present in minority of persons w/XP & may not be detected in young children</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 12 mos for symptomatic patients unless there is new onset of neurologic abnormalities</td></tr><tr><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Hearing</b>
|
|
</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Audiograms</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 6-12 mos</td></tr><tr><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<b>Female</b>
|
|
<br />
|
|
<b>reproductive</b>
|
|
<br />
|
|
<b>system</b>
|
|
</td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Laboratory assessment for premature ovarian insufficiency <sup>1</sup></td><td headers="hd_h_xp.T.recommended_surveillance_for_indivi_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Every 12 mos beginning at age 18 yrs</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="xp.TF.8.1"><p class="no_margin">
|
|
<a class="bibr" href="#xp.REF.merideth.2019.814" rid="xp.REF.merideth.2019.814">Merideth et al [2019]</a>
|
|
</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobxpmolgenTA"><div id="xp.molgen.TA" class="table"><h3><span class="label">Table A.</span></h3><div class="caption"><p>Xeroderma Pigmentosum: Genes and Databases</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.molgen.TA/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.molgen.TA_lrgtbl__"><table class="no_bottom_margin"><tbody><tr><th id="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">Gene</th><th id="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">Chromosome Locus</th><th id="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">Protein</th><th id="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">Locus-Specific Databases</th><th id="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">HGMD</th><th id="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">ClinVar</th></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/1643" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>DDB2</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=1643" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">11p11<wbr style="display:inline-block"></wbr>​.2</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q92466" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA damage-binding protein 2</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/DDB2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DDB2 database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=DDB2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DDB2</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=DDB2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DDB2</a>
|
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</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2067" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
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|
<i>ERCC1</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2067" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">19q13<wbr style="display:inline-block"></wbr>​.32</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P07992" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA excision repair protein ERCC-1</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/ERCC1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC1 database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ERCC1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC1</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ERCC1[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC1</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2068" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ERCC2</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2068" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">19q13<wbr style="display:inline-block"></wbr>​.32</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P18074" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General transcription and DNA repair factor IIH helicase subunit XPD</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.LOVD.nl/ERCC2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC2 @ LOVD</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ERCC2" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC2</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ERCC2[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC2</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2071" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ERCC3</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2071" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">2q14<wbr style="display:inline-block"></wbr>​.3</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P19447" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General transcription and DNA repair factor IIH helicase/translocase subunit XPB</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/ERCC3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC3 database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ERCC3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC3</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ERCC3[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC3</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2072" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ERCC4</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2072" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">16p13<wbr style="display:inline-block"></wbr>​.12</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q92889" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA repair endonuclease XPF</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/ERCC4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC4 database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ERCC4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC4</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ERCC4[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC4</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/2073" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>ERCC5</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=2073" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">13q33<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P28715" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA excision repair protein ERCC-5</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/ERCC5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC5 database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ERCC5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC5</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=ERCC5[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ERCC5</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/5429" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>POLH</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=5429" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">6p21<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q9Y253" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA polymerase eta</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/POLH" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">POLH database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=POLH" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">POLH</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=POLH[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">POLH</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/7507" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>XPA</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=7507" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">9q22<wbr style="display:inline-block"></wbr>​.33</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/P23025" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA repair protein complementing XP-A cells</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/XPA" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">XPA database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=XPA" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">XPA</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=XPA[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">XPA</a>
|
|
</td></tr><tr><td headers="hd_b_xp.molgen.TA_1_1_1_1" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="/gene/7508" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=gene">
|
|
<i>XPC</i>
|
|
</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_2" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/genome/gdv/?context=gene&acc=7508" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">3p25<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_3" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.uniprot.org/uniprot/Q01831" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">DNA repair protein complementing XP-C cells</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_4" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://databases.lovd.nl/shared/genes/XPC" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">XPC database</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_5" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=XPC" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">XPC</a>
|
|
</td><td headers="hd_b_xp.molgen.TA_1_1_1_6" rowspan="1" colspan="1" style="vertical-align:top;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar/?term=XPC[gene]" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">XPC</a>
|
|
</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="xp.TFA.1"><p class="no_margin">Data are compiled from the following standard references: gene from
|
|
<a href="http://www.genenames.org/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HGNC</a>;
|
|
chromosome locus from
|
|
<a href="http://www.omim.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">OMIM</a>;
|
|
protein from <a href="http://www.uniprot.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">UniProt</a>.
|
|
For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click
|
|
<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="figobxpmolgenTB"><div id="xp.molgen.TB" class="table"><h3><span class="label">Table B.</span></h3><div class="caption"><p>OMIM Entries for Xeroderma Pigmentosum (<a href="/omim/126340,126380,133510,133520,133530,278700,278720,278730,278740,278750,278760,278780,600811,603968,610651,611153,613208" 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/NBK1397/table/xp.molgen.TB/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.molgen.TB_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/126340" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">126340</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 2, TFIIH CORE COMPLEX HELICASE SUBUNIT; ERCC2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/126380" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">126380</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 1, ENDONUCLEASE NONCATALYTIC SUBUNIT; ERCC1</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/133510" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">133510</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 3, TFIIH CORE COMPLEX HELICASE SUBUNIT; ERCC3</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<a href="/omim/133520" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">133520</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 4, ENDONUCLEASE CATALYTIC SUBUNIT; ERCC4</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/133530" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">133530</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ERCC EXCISION REPAIR 5, ENDONUCLEASE; ERCC5</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278700" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278700</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A; XPA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278720" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278720</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278730" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278730</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D; XPD</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278740" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278740</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP E; XPE</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278750" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278750</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, VARIANT TYPE; XPV</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278760" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278760</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F; XPF</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/278780" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">278780</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP G; XPG</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/600811" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">600811</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DNA DAMAGE-BINDING PROTEIN 2; DDB2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/603968" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">603968</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">POLYMERASE, DNA, ETA; POLH</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/610651" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">610651</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP B; XPB</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/611153" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">611153</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XPA, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPA</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="/omim/613208" ref="pagearea=body&targetsite=entrez&targetcat=term&targettype=omim">613208</a></td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">XPC COMPLEX SUBUNIT, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPC</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobxpTxerodermapigmentosumnotablepatho"><div id="xp.T.xeroderma_pigmentosum_notable_patho" class="table"><h3><span class="label">Table 9. </span></h3><div class="caption"><p>Xeroderma Pigmentosum: Notable Pathogenic Variants by Gene</p></div><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK1397/table/xp.T.xeroderma_pigmentosum_notable_patho/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__xp.T.xeroderma_pigmentosum_notable_patho_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_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_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Reference<br />Sequences</th><th id="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">DNA Nucleotide Change</th><th id="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Predicted<br />Protein Change</th><th id="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comment [Reference]</th></tr></thead><tbody><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>ERCC2</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_0004000.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000400<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000391.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000391<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.2047C>T</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg683Trp</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Suspected founder variant in Iraqi Jewish population [<a class="bibr" href="#xp.REF.falikzaccai.2012.505" rid="xp.REF.falikzaccai.2012.505">Falik-Zaccai et al 2012</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_1" rowspan="6" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>POLH</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006502.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_006502<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.490G>T <sup>2</sup></td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Accounts for 33% of <i>POLH</i> pathogenic variants in Japanese persons [<a class="bibr" href="#xp.REF.masaki.2008.144" rid="xp.REF.masaki.2008.144">Masaki et al 2008</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006502.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_006502<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_006493.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_006493<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.725C>G</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Ser242Ter</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Accounts for 11% of POLH pathogenic variants in Japanese persons [<a class="bibr" href="#xp.REF.masaki.2008.144" rid="xp.REF.masaki.2008.144">Masaki et al 2008</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006502.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_006502<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.764+1G>A</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Basque region / northern Spain & central Brazil [<a class="bibr" href="#xp.REF.calmels.2016.26" rid="xp.REF.calmels.2016.26">Calmels et al 2016</a>, <a class="bibr" href="#xp.REF.munford.2017.1270" rid="xp.REF.munford.2017.1270">Munford et al 2017</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" rowspan="3" colspan="1" scope="row" style="text-align:left;vertical-align:middle;">
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<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_006502.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_006502<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_006493.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_006493<wbr style="display:inline-block"></wbr>​.1</a>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.916G>T</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Glu306Ter</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Accounts for 20% of <i>POLH</i> pathogenic variants in Japanese persons [<a class="bibr" href="#xp.REF.masaki.2008.144" rid="xp.REF.masaki.2008.144">Masaki et al 2008</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1075-2567_1244+1188del3925<br />(del incl. exon 10)</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asn359ValfsTer32</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Tunisia / North Africa [<a class="bibr" href="#xp.REF.ben_rekaya.2014.256245" rid="xp.REF.ben_rekaya.2014.256245">Ben Rekaya et al 2014</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">c.1664delA<br />(1661delA <sup>3</sup>)</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Asn555ThrfsTer30</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Accounts for 22% of <i>POLH</i> pathogenic variants in Japanese persons [<a class="bibr" href="#xp.REF.masaki.2008.144" rid="xp.REF.masaki.2008.144">Masaki et al 2008</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_1" rowspan="3" scope="row" colspan="1" style="text-align:left;vertical-align:middle;">
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<i>XPA</i>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000380.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000380<wbr style="display:inline-block"></wbr>​.4</a>
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<br />
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000371.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000371<wbr style="display:inline-block"></wbr>​.1</a>
|
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.335_338delTTATinsCATAAGAAA</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Phe112SerfsTer2</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in India [<a class="bibr" href="#xp.REF.tamhankar.2015.16" rid="xp.REF.tamhankar.2015.16">Tamhankar et al 2015</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000380.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000380<wbr style="display:inline-block"></wbr>​.4</a>
|
|
</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.390-1G>C</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">--</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Japan w/carrier frequency of 1% [<a class="bibr" href="#xp.REF.hirai.2006.171" rid="xp.REF.hirai.2006.171">Hirai et al 2006</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" colspan="1" scope="row" rowspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000380.4" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000380<wbr style="display:inline-block"></wbr>​.4</a>
|
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<br />
|
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_000371.1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000371<wbr style="display:inline-block"></wbr>​.1</a>
|
|
</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.682C>T</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Arg228Ter</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in Tunisia [<a class="bibr" href="#xp.REF.messaoud.2010.883" rid="xp.REF.messaoud.2010.883">Messaoud et al 2010</a>]</td></tr><tr><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
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<i>XPC</i>
|
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
|
|
<a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_004628.5" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_004628<wbr style="display:inline-block"></wbr>​.5</a>
|
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<br />
|
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<a href="https://www.ncbi.nlm.nih.gov/protein/NP_004619.3" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_004619<wbr style="display:inline-block"></wbr>​.3</a>
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</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">c.1643_1644delTG</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">p.Val548AlafsTer25</td><td headers="hd_h_xp.T.xeroderma_pigmentosum_notable_patho_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Founder variant in North Africa (Algeria, Morocco, & Tunisia) [<a class="bibr" href="#xp.REF.soufir.2010.1537" rid="xp.REF.soufir.2010.1537">Soufir et al 2010</a>, <a class="bibr" href="#xp.REF.hadjrabia.2013.1109" rid="xp.REF.hadjrabia.2013.1109">Hadj-Rabia et al 2013</a>, <a class="bibr" href="#xp.REF.jerbi.2016.439" rid="xp.REF.jerbi.2016.439">Jerbi et al 2016</a>]</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="xp.TF.9.1"><p class="no_margin">Genes from <a href="/books/NBK1397/table/xp.T.molecular_genetic_testing_used_in_x/?report=objectonly" target="object" rid-ob="figobxpTmoleculargenetictestingusedinx">Table 1</a> are in alphabetic order.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2. </dt><dd><div id="xp.TF.9.2"><p class="no_margin">Results in abnormal splicing [<a class="bibr" href="#xp.REF.masaki.2008.144" rid="xp.REF.masaki.2008.144">Masaki et al 2008</a>]</p></div></dd></dl><dl class="bkr_refwrap"><dt>3. </dt><dd><div id="xp.TF.9.3"><p class="no_margin">Variant designation that does not conform to current naming conventions</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobxpF1"><div id="xp.F1" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1397/bin/xp-Image001.jpg" alt="Figure 1. " /></div><h3><span class="label">Figure 1. </span></h3><div class="caption"><p>Relationship between genotype and phenotype in the xeroderma pigmentosum-Cockayne syndrome-trichothiodystrophy spectrum</p><p>Modified from <a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer [2012]</a></p><p>Italicized letters in purple shapes indicate the genes. Blue rectangles are phenotypes. Because of the complexity of the relationship, it is difficult to predict an individual's phenotype based on the associated gene, in part because specific pathogenic variants have different effects on the overall DNA repair/transcription pathways.</p></div></div></article><article data-type="fig" id="figobxpF2"><div id="xp.F2" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK1397/bin/xp-Image002.jpg" alt="Figure 2. " /></div><h3><span class="label">Figure 2. </span></h3><div class="caption"><p>Nucleotide excision repair (NER) pathway</p><p>Modified from <a class="bibr" href="#xp.REF.digiovanna.2012.785" rid="xp.REF.digiovanna.2012.785">DiGiovanna & Kraemer [2012]</a></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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