013 Pigmentosa xeroderma group D: A clinical and genetic study of 19 Japanese cases

Abstract

Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light with an incidence of 1: 22,000 in Japan. From the clinical symptoms, XP is classified into 3 types, such as XP cutaneous disease, XP neurological disease, and XP/Cockayne syndrome (CS) complex. Genetically, XP is classified into eight distinct groups: A though G and a variant form (V). XPA is the majority (55%) and XPV follows it (25%) in Japanese XP case. Although the frequency of XPD is only 8% in Japan, there are the most diverse clinical symptoms. In contrast to Western XPD reports that there are many cases of XPD neurological disease, there are many patients with XPD cutaneous disease in Japan. In spite of the phenotypic and geographic differences, Japanese XPD cases have not been adequately studied. So, we conducted the clinical, epidemiological, and genetic studies on 19 Japanese XPD cases attended in our institution from 1998 to 2017 using medical records, referral letters, and laboratory data. The mean age at which a final diagnosis of XPD was 35.6 years old and all patients had a history of sunburn. In the clinically analysis, there were 15 cases of XPD cutaneous disease, 1 case of XPD neurological disease, and 3 cases of XP/CS complex. Twelve of the 19 cases had complications of skin malignancies. The age at onset of skin cancer was 44.4 years for cutaneous disease, 12 years for neurological disease, and 2 years for XP/CS complex. By the genetic analysis, we assumed that R601L was associated with cutaneous disease, G47R was associated with severe XP/CS complex, and R636W was associated with mild XP/CS complex. In conclusion, we have conducted the clinical, epidemiological, and genetic studies on 19 Japanese XPD cases. The type of XPD cutaneous disease is dominant in Japanese XPD cases. And clinical type (phenotype) / genotype association is implied in Japanese XPD patients from the confirmed gene mutation.