Neurodegeneration in Xeroderma Pigmentosum: a trinucleotide repeat mutation analysis.

Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder caused by defects in DNA repair. In some forms, it is clinically and pathologically characterized by neurological involvement and premature neuronal death. This study explores the hypothesis that defects in DNA repair in XP may contribute to neurological involvement by destabilizing trinucleotide repeats during replication causing expansion mutations into disease producing ranges. Trinucleotide repeat instability in each of the genes causing Machado-Joseph Disease, myotonic dystrophy, Kennedy's Disease and Huntington's Disease was analyzed by performing single genome PCR. The results of trinucleotide repeat analysis of 360 single genomes from three different forms of XP showed that the size of the repeats were in the normal range and that there was no mitotic instability. These results suggest that in XP, trinucleotide repeat expansion mutations are not involved in the pathophysiology of neurodegeneration.