Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation

Expansion of CTG/CAG trinucleotide repeats has been shown to cause a number of autosomal dominant cerebellar ataxias (ADCA) such as SCA1, SCA2, SCA3/ MJD, SCA6, SCA7, SCA8 and DRPLA. There is a wide variation in the clinical phenotype and prevalence of these ataxias in different populations. An anal ysis of ataxias in 42 Indian families indicates that SCA2 is the most frequ ent amongst all the ADCAs we have studied. In the SCA2 families, together w ith an intergenerational increase in repeat size, a horizontal increase wit h the birth order of the offspring was also observed, indicating an importa nt role for parental age in repeat instability. This was strengthened by th e detection of a pair of dizygotic twins with expanded alleles showing the same repeat number. Haplotype analysis indicates the presence of a common f ounder chromosome for the expanded allele in the Indian population. Polymor phism of CAG repeats in 135 normal individuals at the SCA loci studied show ed similarity to the Caucasian population but was significantly different f rom the Japanese population.