Xeroderma pigmentosum patients from Egypt: II. Preliminary correlations of epidemiology, clinical symptoms and molecular biology.
Xeroderma pigmentosum (XP) occurs with high frequency in Egypt and a continuation of our field studies has identified representatives of the 3 major complementation groups A, C, and variant. Group A patients, with one exception, showed very early onset of sun sensitivity and development of skin cancers, and microcephaly and mental retardation. The exceptional group A patient was 35 yr old, with normal stature and intelligence who had 2 normal children. DNA repair was as low in his cells as in other group A cases. Group C patients showed a slightly slower onset of sun sensitivity and had no central nervous system disorders. The variants showed later onset of sun sensitivity and no skin cancers evident at the time of observation (about 20 yr of age). No sun sensitivity was present in the 25 heterozygotes we observed, nor reportedly in the additional 60 not yet observed. This indicates that only homozygosity for XP genes increases risk of skin cancer. Cell cultures from both normal persons and these XP patients reached in vitro "senescence" at similar passage levels. Groups A and C appear to have lost different major gene products that are involved in the excision of UV damage from DNA, but the residual repair in XP-C cells facilitates more recovery of DNA synthesis than in other groups. This may contribute to the higher in vitro survival in culture and milder clinical symptoms in group C as compared to group A. XP variants appear to have lost a gene product that permits normal cells to replicate, uninterrupted by DNA damage, and consequently synthesize DNA in smaller pieces than normal.
D000328:Adult; D002478:Cells, Cultured; D003165:Complement System Proteins; D004260:DNA Repair; D004261:DNA Replication; D004534:Egypt; D005260:Female; D006801:Humans; D008297:Male; D014983:Xeroderma Pigmentosum / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*
D003165:Complement System Proteins