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Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). 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). Treatment of manifestations: Small, 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. 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 transplantation may improve the visual impairment resulting from severe keratitis. Hearing loss may be treated with hearing aids. Prevention of primary manifestations: Avoid sun and other UV exposure to the skin and eyes; measurement of UV light with a light meter in an individual's home, school, and/or work environment so that high levels of environmental UV can be identified and eliminated. Prevention of secondary complications: Dietary supplementation with oral vitamin D as needed.

Surveillance: Skin examinations by a physician every three to 12 months; periodic routine eye and neurologic examinations and audiograms. Agents/circumstances to avoid: UV exposure from sunlight and artificial sources of UV radiation, cigarette smoke.

Evaluation of relatives at risk: If family-specific pathogenic variants have been identified, of at-risk sibs can permit early diagnosis and rigorous sun protection from an early age. Pregnancy management: 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. Establishing the Diagnosis The diagnosis of XP is established in a on the basis of clinical findings and family history (see ) and/or by the identification of pathogenic variants in one of the genes listed in.

Molecular testing approaches can include serial single- testing, use of a, and more comprehensive testing. Serial single testing. The choice of which genes to analyze can be guided by the clinical features and the relative frequency in the population where the individual was born (see,,, and ). Basque / Northern Spain: c.764+1G>A [] A that includes DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, and XPC and other genes of interest (see ) may also be considered.

Note: (1) The genes included and the of multigene panels vary by laboratory and over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost. (3) Methods used in a panel may include,, and/or other non-sequencing-based tests. For more information on multigene panels click. More comprehensive testing (when available) including and may be considered if serial single- testing (and/or use of a that includes DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, POLH, XPA, and XPC) fails to confirm a diagnosis in an individual with features of XP.

Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). For more information on comprehensive genomic testing click. Gene 1 Proportion of XP Attributed to Pathogenic Variants in This Gene 2 Proportion of Pathogenic Variants 3 Detectable by Test Method US Japan Europe Sequence analysis 4 Gene-targeted 5 DDB2 3% 3% 15/15 alleles 6 Unknown 7 ERCC1 Rare 4/4 alleles 8 Unknown ERCC2 28% 5% 16% >99% Unknown ERCC3 1% 0% 2% 8/8 alleles 9 Unknown ERCC4 10 0% 7% 3% ~99% Rare 11 ERCC5 3% 1% 9% >99% Unknown POLH 7% 25% 13% 25/40 alleles; 33/42 alleles 12 15/40 alleles; 9/42 alleles 12 XPA 9% 55% 13 20% 100% Unknown XPC 43% 3% 31% 7/12 alleles 14 5/12 alleles 14. Continued sun exposure causes the skin to become dry and parchment-like with increased pigmentation; hence the name xeroderma pigmentosum ('dry pigmented skin'). Most individuals with XP develop xerosis (dry skin) and poikiloderma (the constellation of hyper- and hypopigmentation, atrophy, and telangiectasia). Premalignant actinic keratoses develop at an early age. XP is an example of accelerated photo-aging.

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. Ocular abnormalities are almost as common as the cutaneous abnormalities [, ]. Findings may begin in the first decade of life and are usually limited to the anterior, UV-exposed portions of the eyes: conjunctiva, cornea, and lids [, ]. The benign conjunctival inflammatory masses that develop can spread to obscure the cornea. Epithelioma, squamous cell carcinoma, and melanoma of UV-exposed portions of the eye are common. The ocular manifestations may be more severe in black individuals [,, ]. Progressive neurologic abnormalities that worsen slowly were reported in approximately 25% of 106 individuals [,,,,, ].

The onset may be early in infancy or, in some individuals, delayed until the second decade or later []. The neurologic abnormalities may be mild (e.g., hyporeflexia) or severe, with microcephaly, progressive intellectual impairment, sensorineural hearing loss beginning with high frequencies, spasticity, ataxia, and/or seizures. During an upper respiratory infection some individuals may develop difficulty swallowing or, rarely, vocal cord paralysis []. Surprisingly, the persons with XP with the most severe sun sensitivity had a later onset of skin cancer – probably because they used greater sun protection. Other neoplasias.

Review of the world literature has revealed a substantial number of people with XP who have oral cavity neoplasms, particularly squamous cell carcinoma of the tip of the tongue, a presumed sun-exposed location [,, ]. 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 [,,, ]. Because some of the carcinogens in cigarette smoke bind to DNA resulting in damage that is repaired by the nucleotide excision repair (NER) system, this unrepaired DNA damage may contribute to the development of lung cancer in individuals with XP.

Overall, these reports suggest an approximate ten- to 20-fold increase in internal neoplasms in XP [,, ]. Causes of death. The most common causes of death were skin cancer (34%, n=10); neurologic degeneration (31%, n=9); and internal cancer (17%, n=5). 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). Nomenclature 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 and in. Previously, an individual with XP with any neurologic abnormality was said to have the DeSanctis-Cacchione syndrome. With clarification of the spectrum of XP disease, this term is now reserved for XP with severe neurologic disease with 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.

'Pigmented xerodermoid' is now known to be identical to the XP variant. Before the genes responsible for XP were identified, complementation groups were used to categorize functional defects in 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. 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 (). Testing to assign complementation group is currently not commercially available. Described a male age 15 years with cachexia, dwarfism, and 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. Proposed that this represented a new progeroid syndrome. Whether XFE progeroid syndrome represents a distinct condition or is part of the spectrum of XP, FA, or XP/CS has not been determined.

Sporadic tumors. Investigation of the association between an increased cancer risk and heterozygosity for an allelic variant causing XP is an active area of research. Phenotype 1 Gene(s) Clinical Features Cerebrooculofacioskeletal (COFS) syndrome (Pena-Shokeir syndrome, type II; OMIM ) ERCC2 2 ERCC5 2 ERCC6 3 Progressive neurologic disorder marked by microcephaly w/intracranial calcifications & growth failure.

Ocular findings of microcornea, cataracts, & optic atrophy are present along w/ joint contractures. Photosensitivity may occur w/a concurrent cellular of UV sensitivity. (CS) ERCC6 ERCC8 4 CS type I: Normal prenatal growth w/onset of growth & developmental abnormalities in the first 2 years. By the time the disease has become fully manifest, height, weight, & head circumference are far below the 5th percentile.

Progressive impairment of vision, hearing,& central & peripheral nervous system function lead to severe disability. Death typically occurs in the 1st or 2nd decade. As in XP, cells from individuals w/CS are hypersensitive to killing by UV; however, CS cells have normal post-UV unscheduled DNA synthesis (UDS). CS cells also have delayed recovery of RNA synthesis after UV exposure, reflecting their deficiency in transcription-coupled nucleotide excision repair (TC-NER). Hartnup disorder (OMIM ), a disorder of amino acid absorption resulting from pathogenic variants in SLC6A19, a non-polar amino acid transporter. 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. The cutaneous findings of may be confused with those of XP; however, Carney complex is characterized by lentigines without evidence of the usually associated signs of skin damage such as atrophy and telangiectasia (i.e., poikiloderma) and cutaneous findings are not limited to sun-exposed sites []. Treatment of Manifestations The treatment of manifestations is reviewed in and. Premalignant lesions (e.g., small actinic keratosis) may be treated by freezing with liquid nitrogen.

Larger areas of sun-damaged skin can be treated with field treatments such as topical 5-fluorouracil or imiquimod preparations. Rarely, therapeutic dermatome shaving or dermabrasion has been used to remove the more damaged superficial epidermal layers. This procedure permits repopulation by relatively UV-shielded cells from the follicles and glands.

Cutaneous neoplasms are treated in the same manner as in individuals who do not have XP. This involves electrodesiccation/curettage or surgical excision. Skin cancers which are recurrent or in locations at high risk for recurrence are best treated with Mohs micrographic surgery. Because multiple surgical procedures are often necessary, removal of undamaged skin should be minimized. Severe cases have been treated by excision of large portions of the facial surface and grafting with sun-protected skin. While individuals with XP are not abnormally sensitive to therapeutic x-rays, and individuals with XP have responded normally to full-dose therapeutic x-radiation for treatment of inoperable neoplasms [], cultured cells from a few individuals with XP were found to be hypersensitive to x-radiation []. When x-radiation therapy is indicated, an initial small dose is advisable to test for clinical hypersensitivity.

Oral isotretinoin or acitretin can be effective in preventing new neoplasms in individuals with multiple skin cancers []. Because of its toxicity (hepatic, hyperlipidemic, and teratogenic effects; calcification of ligaments and tendons; premature closure of the epiphyses), oral isotretinoin or acitretin should be reserved for individuals with XP who are actively developing large numbers of new tumors. Some individuals may respond to lower doses of isotretinoin or acitretin with less toxicity. A few case reports have described regression of skin cancers with use of imiquimod cream in individuals with XP [,, ]; however, no controlled studies have been reported. Methylcellulose eye drops or soft contact lenses have been used to keep the cornea moist and to protect against mechanical trauma in individuals with deformed eyelids. Corneal transplantation has restored vision in individuals with severe keratitis with corneal opacity. However, the immunosuppression necessary to prevent rejection of the transplant may increase the risk for skin cancer.

Neoplasms of the lids, conjunctiva, and cornea are usually treated surgically. Hearing aids can be of great help for individuals who have sensorineural hearing loss with learning difficulties in school (see and ). Prevention of Primary Manifestations 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). Clinical suspicion of XP should prompt immediate sun-protective measures until the diagnosis is confirmed or an alternative explanation is determined. 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 sun-protective factor (SPF) sunscreens, UV-absorbing glasses, and long hair styles. 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. 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. Prevention of Secondary Complications 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) []. 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 [; Author, personal observation].

Dietary supplementation with oral vitamin D is recommended for persons with low serum concentration of serum vitamin D [; Author, personal communication]. Surveillance See and.

A physician should examine the skin of an individual at frequent intervals (every ~3-12 months, depending on the severity of skin disease). Affected individuals or their parents should be educated to look for abnormal pigmented lesions or the appearance of basal cell or squamous cell carcinoma. Individuals should be examined frequently by a family member who has been instructed in recognition of cutaneous neoplasms. Eyes should be examined regularly for signs of UV exposure and damage.

Routine neurologic examination is indicated because of progressive neurologic abnormalities that are present in a minority of individuals with XP and may not be detected in young children. Periodic audiograms. Serial audiograms at regular intervals may also be useful for assessing the presence or absence of progressive neurologic degeneration, especially in those with a history of acute burning on minimal sun exposure []. Agents/Circumstances to Avoid UV exposure from sunlight and artificial sources of UV radiation should be avoided (see ). Artificial sources of UV. 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.

Cigarette smoke. Because cells from individuals with XP are also hypersensitive to environmental mutagens, such as benzo[ a]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 []. The authors recently cared for another individual with XP who smoked and developed lung cancer in the fifth decade of life.

Pregnancy Management 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 []. 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. To access isotretinoin in the US, women and their prescribing providers must be enrolled in the 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 drugs 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.

Therapies Under Investigation The bacterial DNA repair enzyme T4 endonuclease V in a topical liposome-containing preparation has been reported to reduce the frequency of new actinic keratoses and basal cell carcinomas in individuals with XP in one research study []. As of 2016, this treatment is not approved by the US Food and Drug Administration. Oral vismodegib (Erivedge ®), an inhibitor of the hedgehog pathway, has been approved by the FDA for treatment of metastatic basal cell carcinoma or locally advanced basal cell carcinoma that has recurred following surgery. This drug has also been approved for use in individuals with basal cell carcinoma who are not candidates for surgery or for radiation therapy (see ). This treatment may be appropriate for some individuals with XP, however, no studies on the efficacy of this drug in those with XP have been published. Oral vismodegib is also a teratogen, leading to embryo-fetal death, midline defects, missing digits, and other birth defects in an exposed embryo or fetus; effective contraception during and after vismodegib treatment is advised in both women and men.

Search for access to information on clinical studies for a wide range of diseases and conditions. Genetic Counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. Nucleotide excision repair (NER) pathway Modified from DiGiovanna & Kraemer [2012] 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 DDB2-encoded protein [, ]. The XPC-encoded protein binding to the photoproducts is facilitated by the binding of the DDB2-encoded protein. The XPC-encoded protein is complexed with hHR23B and centrin []. DNA damage in transcribed genes (transcription coupled repair [TCR]) is marked by stalled RNA polymerase. The CS encoded proteins (along with others) bind to the damage in the transcribed DNA strand. In both global genome repair and transcription coupled repair the XPA protein probably functions in conjunction with replication protein A (RPA), and TFIIH.

The XPB/ERCC3 and XPD/ERCC2 proteins (helicases which 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 [, ]. The nucleotide excision repair genes (e.g., XPB/ ERCC3 and XPD/ ERCC2) that are part of the basal TFIIH are essential to life. Mice with knockout of Ercc2 do not survive, whereas Xpa and Xpc knockout mice are viable.

For detailed summary of and protein information for the genes listed below, see, Gene. DDB2 ( XPE) Gene structure. DDB2 codes for a 1.8-kb RNA. It comprises ten exons and nine introns (). Pathogenic variants. Missense,, and frameshift variants have been reported [,, ] (see also ). DDB2 codes for a 48-kd protein of 427 amino acids. 3d Map Of India Download.

DDB2 combined with DDB1 forms a heterodimer, which, along with XPC, is involved in the initial recognition of UV-induced DNA damage in non-transcribed portions of the genome. XP results from absent. Loss of the p48 subunit encoded by DDB2 results in large numbers of skin cancers without acute burning on minimal sun exposure [, ].

ERCC2 ( XPD) Gene structure. ERCC2 codes for a 2.3-kb.

It comprises 22 exons and 21 introns (). Pathogenic variants. Individuals with pathogenic variants in ERCC2 exhibit significant. Missense variants with resulting change in amino acids with some residual activity [] are frequently found in cells from individuals with XP-D []. The p.Arg683Trp is common in the Iraqi Jewish population [] and occurs at a. The p.Arg683Gln pathogenic variant has been reported in individuals with XP in many parts of the world [, ] (see also ).

Individuals with pathogenic variants in ERCC2 may have an XP, TTD, or XP/TTD []. A mild was reported in Israel []. Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (). See for an explanation of nomenclature. ERCC2 codes for an 86.9-kd protein of 760 amino acids. ERCC2, like the ERCC3 (XPB) protein, is also a DNA helicase (but unwinds DNA in the 5'- 3' direction).

ERCC2 is part of basal TFIIH that is involved in regulation of the basal rate of transcription (RNA synthesis) of active genes, as well as in NER. XP results from absent. Abnormal ERCC2 in persons with XP results in persistent NER protein accumulation at sites of DNA damage while abnormal ERCC2 in persons with TTD results in failure of accumulation of NER proteins at sites of localized DNA damage []. ERCC3 ( XPB) Gene structure. ERCC3 codes for a 2.75-kb. It comprises 15 exons and 14 introns ().

Pathogenic variants. Nonsense, frameshift, and defects have been reported [, ] (see also ). ERCC3 codes for an 89.3-kd protein of 782 amino acids that functions as a 3'- 5' DNA helicase in unwinding DNA. The ERCC3-encoded protein is part of the TFIIH complex, which is involved in regulation of the basal rate of transcription (RNA synthesis) of active genes, as well as in nucleotide excision repair. XP results from absent or inactivated protein. Affected individuals have severe disease with neurologic involvement or mild disease without neurologic involvement [, ]. ERCC4 ( XPF) Gene structure.

ERCC4 codes for a 6.7-kb. It comprises 11 exons and ten introns (). Pathogenic variants. Missense variants have been reported [] (see also ).

ERCC4 codes for a 103.3-kd protein of 905 amino acids that serves as a DNA endonuclease 5' to the lesion. XP results from absent or inactivated.

Loss of XPF may result in mild disease or adult onset of severe neurologic degeneration [Author, personal observation], or features of FA, CS, XP/CS complex, and XP/CS/FA. See also [,, ].

ERCC5 ( XPG) Gene structure. ERCC5 codes for a 4.1-kb (). It comprises 15 exons and 14 introns []. Pathogenic variants.

Missense,, frameshift, and variants have been reported [] (see also ). One individual with pathogenic variants in ERCC5 ( XPG) and minimal neurologic involvement developed retinal atrophy and basal ganglia calcification of the XP/CS complex while being followed at the NIH []. ERCC5 codes for a protein of 112 kd that functions as a DNA endonuclease 3' to the lesion. XP results from absent or inactivated. Pathogenic variants resulting in markedly truncated ERCC5 are found in individuals with XP-G with the XP/CS complex, while individuals with XP-G without neurologic disease have variants that retain some activity [,, ]. XPA Gene structure.

XPA codes for a 1.4-kb. It comprises six exons and five introns (). Pathogenic variants.

A pathogenic founder creating a variant in 3 of XPA, c.390-1G>C, is estimated to occur at a frequency of approximately 1% of the Japanese population. Individuals who are for this allele have severe, progressive neurologic degeneration; carriers are clinically normal [, ]. This appeared in the Japanese population approximately 120 generations (~2400 years) ago []. Persons of Japanese heritage who are compound heterozygotes for this XPA variant and a second XPA variant have milder disease than those who are homozygous for the founder variant [] (see also ).

A variant, p.Arg228Ter, is common in the Tunisian population and results in mild disease []. Although other common pathogenic alleles have been described in population isolates, most pathogenic alleles are. Nonsense variants have been reported in both alleles in cells from individuals in complementation group XP-A. Mild clinical features were found in an individual with an XPA variant resulting in 5% of normal residual []. Variants near the C-terminal of XPA had milder neurologic and cutaneous symptoms and greater residual DNA repair activity in several Japanese persons with XP []. XPC Gene structure. XPC codes for a 3.5-kb ().

It comprises 16 exons []. Pathogenic variants. Nonsense,, and frameshift variants have been reported in both alleles in cells from individuals in complementation group XP-C. Pathogenic variants are less frequent [, ] (see also ). P.Val548AlafsTer25, a in XPC resulting in severe disease, was reported in persons with XP from North Africa (Algeria, Morocco, and Tunisia) [,,, ]. Haplotype analysis suggested that this variant arose about 50 generations (1250 years) ago [].

The frequency of the African XPC founder variant is not known. Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (). See for an explanation of nomenclature.

XPC codes for a 105.9-kd protein of 940 amino acids. The XPC protein is involved with recognition of DNA damage and global genome repair. XP results from absent or inactivated. Individuals with XPC splice lariat variants may have severe or mild disease [, ]: those with mild disease have about 3% of normal residual XPC while those with severe disease have no detectible XPC mRNA. Persons with pathogenic variants in XPC typically do not have acute burning on minimal sun exposure []. © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle.

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