Novel germline ERCC5 mutations identified in a xeroderma pigmentosum complementation group G pedigree.

CS: Cockayne syndrome ERCC5: Excision Repair Cross-complementing Rodent Repair Deficiency Complementation Group 5 gene NER: Nucleotide excision repair UV: Ultraviolet WES: Whole exome sequencing XP: Xeroderma pigmentosum XP-G: Xeroderma pigmentosum complementation group G INTRODUCTION Xeroderma pigmentosum (XP) is an autosomal recessive genodermatosis caused by a germline loss of function in DNA repair enzymes. This defect impairs physiologic DNA repair after ultraviolet (UV) radiationeinduced damage, which can lead to photosensitivity in about half of all patients, pigmentation abnormalities, and an increased risk of nonmelanoma skin cancers as well as melanoma. XP patients classically exhibit a 10,000-fold increase in the frequency of skin cancers arising in sunexposed skin, eyes, and other mucosal areas (eg, lips and tongue), which appear at an early age. Prognosis and mortality of XP patients are mostly tightly related to the risk of metastasis of cutaneous squamous cell carcinomas and melanomas but also depend on the extent of the underlying DNA repair deficiency. The life expectancy of XP patients is reduced by 30 years. Seven genetically distinct complementation groups of XP (designated XP-A through XP-G depending on the gene mutated) with germline loss of function mutations to enzymes are involved in nucleotide excision repair (NER). The degree of photosensitivity, risk of skin cancer, and risk of neurologic abnormality vary from complementation group to group. XP complementation group G