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. Thi s study explores the hypothesis that defects in DNA repair in XP may contri bute to neurological involvement by destabilizing trinucleotide repeats dur ing replication causing expansion mutations into disease producing ranges. Trinucleotide repeat instability in each of the genes causing Machado-Josep h Disease, myotonic dystrophy, Kennedy's Disease and Huntington's Disease w as analyzed by performing single genome PCR. The results of trinucleotide r epeat analysis of 360 single genomes from three different forms of XP showe d 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 rep eat expansion mutations are not involved in the pathophysiology of neurodeg eneration. (C) 1999 Elsevier Science B.V. All rights reserved.