Pathological repeat variation at the SCA17/TBP gene in south Indian patients

Despite the intense debate around the repeat instability reported on the large group of neurological disorders caused by trinucleotide repeat expansions, little is known about the mutation process underlying alleles in the normal range, diseases range, large normal alleles (LNAs). In this study, we assessed the CAG repeats at SCA17 in 188 clinical SCA patients and 100 individuals without any neurological signs. This highly polymorphic population displayed high variability in the CAG repeats and ranged from 19-38 CAG repeats in patients with mode of 20 and 19-32 CAG repeats in controls with mode of 24. The triplet repeat expansion was not detected in any of the 188 patients, as per the reference pathogenic range (>43 repeats); however, 2.7% of the patients had >33 CAG repeats with a clinical phenotype close to what is expected of SCA 17 patients. The findings of this study implicate a more sophisticated interpretation of SCA17 gene and raise the question about the diagnostic thresh hold between normal and expanded repeats in our population.