Whole-exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39-year-old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle-like pigmented macules in sun-exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen's disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole-exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu inERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient's fibroblasts recovered only when they were transfected withXPDcDNA, confirming the diagnosis of XP-D. Arg601Leu mutation inERCC2may be related to mild UV radiation sensitivity and moderate skin lesions.

Automated summary

A case of xeroderma pigmentosum (XP) group D in a 39-year-old Japanese man was reported, with manifestations of early skin lesions and malignant skin tumors. The patient was found to harbor an Arg601Leu mutation in ERCC2, which may be related to mild UV radiation sensitivity and moderate skin lesions.