Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions

Sethi, Mieran; Lehmann, Alan R.; Fawcett, Heather; Stefanini, Miria; Jaspers, Nicolaas G. J.; Mullard, Kenneth S.; Turner, Steven; Robson, Alistair; McGibbon, David; Sarkany, Robert; Fassihi, Hiva

doi:10.1111/bjd.12523

Cited by 67 publications

(69 citation statements)

References 29 publications

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“…iii) In contrast, the first symptoms in XP-C patients are photodistributed lentigines around the age of 2 y. They have a later age of XP diagnosis and therefore accumulate more photodamage, leading to an earlier age of first skin cancer (4,5). iv) XP-E and XP-V patients tend to be diagnosed much later; they may have two decades or more without any symptoms.…”

Section: Resultsmentioning

confidence: 99%

“…16 and much of the sunburn data have been presented in ref. 5. These data are reproduced here for completeness.…”

Section: Xp-b (Mim610651)mentioning

confidence: 92%

“…*UDS is measured, after a UVC dose of 10 J·m −2 , as percent of that in normal cells used as control in the same experiment. BCC, basal cell carcinoma; MIS, melanoma in situ; MM, malignant melanoma; ND, not done; NMSC, nonmelanoma skin cancer; SCC, squamous cell carcinoma; SSS, sunburn severity score (5). Note that the mutation data for the XP-A patients has been presented in ref.…”

Section: Xp-b (Mim610651)mentioning

confidence: 99%

“…XP patients have a 2,000-and 10,000-fold increased incidence of melanoma and nonmelanoma skin cancers, respectively (4). About 50% of XP patients show severe sunburn reactions on minimal sun exposure (5), and approximately one third of patients have progressive neurological degeneration associated with neuronal loss (4,5). XP has been intensively studied at the molecular and cellular levels, as affected individuals are defective in the repair of UV radiation (UVR)-induced DNA damage.…”

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confidence: 99%

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Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Fassihi

Sethi

Fawcett

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

165

202

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Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins.UV radiation | nucleotide excision repair | skin cancer | ocular disease | neurodegeneration

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Section: Resultsmentioning

confidence: 99%

“…16 and much of the sunburn data have been presented in ref. 5. These data are reproduced here for completeness.…”

Section: Xp-b (Mim610651)mentioning

confidence: 92%

Section: Xp-b (Mim610651)mentioning

confidence: 99%

mentioning

confidence: 99%

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Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Fassihi

Sethi

Fawcett

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

165

202

View full text Add to dashboard Cite

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“…Neurological manifestations occur in 20–30% of cases,4 usually after the cutaneous signs. Cognitive impairment, cerebellar signs, sensorineural hearing loss, and sensorimotor axonal neuropathy have been reported 6, 9. In advanced cases, movement disorders may appear 7, 8, 10…”

Section: Introductionmentioning

confidence: 99%

Xeroderma pigmentosum is a definite cause of Huntington's disease‐like syndrome

García-Moreno

Fassihi

Sarkany

et al. 2017

Ann Clin Transl Neurol

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Xeroderma pigmentosum is characterized by cutaneous, ophthalmological, and neurological features. Although it is typical of childhood, late presentations can mimic different neurodegenerative conditions. We report two families presenting as Huntington's disease‐like syndromes. The first case (group G) presented with neuropsychiatric features, cognitive decline and chorea. Typical lentigines were only noticed after the neurological disease started. The second case (group B) presented adult‐onset chorea and neuropsychiatric symptoms after an aggressive ocular melanoma. Xeroderma pigmentosum can manifest as a Huntington's Disease‐like syndrome. Classic dermatological and oncological features have to be investigated in choreic patients with negative genetic tests for Huntington's disease‐like phenotypes.

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DNA Repair Disorders with Cutaneous Features

Fassihi

2016

Rook's Textbook of Dermatology, Ninth Edition

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The human genome is continually being damaged by a variety of sources (such as reactive oxygen species and ultraviolet and ionizing radiation). Cells have evolved a number of complex pathways (nucleotide excision repair, double strand break repair and mismatch repair) to recognize and repair this damage in actively transcribed genes. Defects in these pathways result in a number of disorders, many with skin involvement, commonly photosensitivity, cancer and premature ageing. Xeroderma pigmentosum (XP), Cockayne syndrome and trichothiodystrophy are caused by defects in the nucleotide excision repair. All three syndromes can show photosensitivity because of an inability to repair UV radiation‐induced DNA damage. However, they are clinically very heterogeneous and only patients with XP have an increased risk of skin cancer. Early accurate diagnosis, based on clinical features, assessment of DNA repair and genetic analysis, can significantly improve morbidity and mortality from skin cancers, and also enables appropriate genetic counselling and prenatal diagnosis.

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Patients with xeroderma pigmentosum complementation groups C, E and V do not have abnormal sunburn reactions

Cited by 67 publications

References 29 publications

Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Xeroderma pigmentosum is a definite cause of Huntington's disease‐like syndrome

DNA Repair Disorders with Cutaneous Features

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