CLINICAL, GENETIC AND DNA-REPAIR STUDIES ON A CONSECUTIVE SERIES OF PATIENTS WITH XERODERMA PIGMENTOSUM

  • 1 January 1979
    • journal article
    • research article
    • Vol. 48  (190) , 179-210
Abstract
Clinical, genetic and biochemical findings were reported in 13 families with the photosensitive genodermatosis, xeroderma pigmentosum [XP]. All patients had a defect in repair of DNA damage provoked by UV radiation [UVR]. Eleven patients and their 3 affected sibs were defective in the excision repair of UVR-induced DNA lesions while the other 2 were defective in post-replication repair. One in the former group was diagnosed prior to the development of permanent skin abnormalities and preventive measures succeeded for almost 5 yr in maintaining a normal appearing skin. In addition, 2 cases were diagnosed prenatally and aborted therapeutically. Some patients'' parents showed slightly reduced repair of UVR-induced DNA damage. XP, the defect in the excision of DNA lesions, appears to be due to homozygosity for 1 of at least 7 different mutations; accordingly, XP patients can be assigned to 7 so-called complementation groups, A to G. Of these, groups A, C and D are the most common. Somatic cell fusion allowed 3 of the families reported here to be assigned to group A, 4 to group C and 4 to group D. Fibroblasts of patients from these 3 groups were shown to differ in the degree and kinetics of their residual DNA repair and in the kinetics with which their defect is complemented by fusion with normal or XP cells of other groups. This confirms that mutations of different genes play a role in XP and provide a basis for understanding how such genes interact to secure repair of DNA lesions in normal cells. The phenotype of XP from different complementation groups is discussed in relation to the severe neurological abnormalities which may develop and must be considered in genetic counseling. The biochemical anomalies of XP and the cellular effects of physical and chemical agents which damage DNA were also considered. In the practical management of XP, the importance of early differential diagnosis and prompt initiation of treatment is emphasized. The relationship between DNA repair and skin cancer in XP is reviewed.

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