[Neurological manifestations and molecular basis of group A xeroderma pigmentosum]

The molecular basis of group A xeroderma pigmentosum (XP) was investigated by Southern blot analysis of genomic DNA and Northern blot analysis of poly (A)+ RNA from patients with group A and atypical group A XP and normal controls. The clones of a patient with group A XP who had typical symptoms showed a G-->C substitution at the 3' splice acceptor site of intron 3, which is the most common mutation in Japanese group A XP patients. On the other hand, one typical group A patient and one atypical group A patient with mild skin lesions and minimal neurological abnormalities showed compound heterozygote for the splicing mutation of intron 3 and the nonsense mutation of exon 6. The other one atypical group A patient showed a homozygote of the nonsense mutation of exon 6, thus suggesting no direct correlationship between severity of neurological complication and DNA abnormality. Northern blot analysis of poly (A)+ RNA revealed that the XPAC mRNAs of group A XP cells were smaller than that of normal controls, and amounts were markedly reduced. Of three atypical group A XP patients, one showed almost normal size and amount of the XPAC mRNA, another showed as small size and reduced amount of the XPAC mRNA, while the third one showed an intermediate type between typical group A XP and normal controls.