Clinical symptoms and molecular basis of group a xeroderman pigmentosum

Abstract

The molecular basis of group A xeroderman pigmentosum (XP) was investigated by Southern blot analysis of genomic DNA for allelic heterogeneity in group A XP and comparison of clinical symptoms and severity of neurological complications. As previously reported, tow group A XP patients (XP-YK and XP-HH) with mild skin lesions and minimal neurological abnormalities had different mutations, one was a homozygote for the nonsense mutation of exon 6 (XP-YK), while the other was a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6 (XP-HH). The present study revealed that one typical group A XP patient with severe skin lesions and severe neurological complications also was a compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6, thus suggesting the nonsense mutation of exon 6 is not always associated with mild skin lesions nor mild neurological manifestations. Further investigation of the sensitivity to UV radiation of fibroblasts from two atypical group A XP patients (XP-YK and XP-HH) with mild skin lesions and minimal neurological abnormalities showed intermediate post-UV colony-forming ability between that of typical group A and group C XP patients. These results suggest that DNA abnormalities are not always consistent with the severity of clinical symptoms, and that mild clinical symptoms may be explained by the residual ability of the cells to repair UV-damaged DNA.