Molecular Analysis of CTG/CTA Repeats at SCA8 Locus in South Indian Population

Abstract

Spinocerebellar ataxias are a group of phenotypically and genetically heterogenous disorders characterized by progressive degeneration of the cerebellum with overlapping symptoms. A novel form of SCA has been described with triplet repeat expansions in the 3 UTR of the SCA8 gene and is caused by expansion of a CTG/CTA repeat in the ataxin-8 opposite strand gene (ATXN8OS) located on chromosome 13q21. Analysis of CTA/CTG repeats in SCA8 gene was performed in 188 ataxia patients and 100 healthy volunteers without any neurological signs or family history. The repeat length was found to be highly polymorphic. We were unable to find any individual with pathogenic repeat length in SCA8 gene, when we used the already established pathogenic repeat criteria. However, repeats >35 (4.7%) were exclusively found in patients only and none of the controls suggesting that these repeat sizes could be pathogenic for our population. The frequency of LN alleles was also found to be higher than reported for other populations. The percentage of LN alleles at SCA 8 locus was 65% and 47% in patients and controls. In the present study three patients also exhibited repeats lower than the normal range and the pathological implications of these needs to be explored.