Polymorphic study of ataxin 3 gene in Eastern Uttar Pradesh population

Abstract

Introduction: Spinocerebellar ataxia type 3 (SCA3), or Machado-Joseph disease (MJD), is a prevalent autosomal dominant-inherited disease that causes progressive problems with movement. Abnormal repetitive expansion of CAG trinucleotide in the ATXN3 gene results in SCA3. This study was done to review the corporation of CAG repeats and polymorphisms in definitive genes with the occurrence of SCA3 in the Indian community, especially in the eastern UP population. Material and Methods: The 40 Ataxia's patient and their parents were listed after obtaining written consent from the participant's attendant/guardians. Out of these, we have identified polymorphism in three patients. Results: In one patient, we have found a single base change, g.31483A>T in Exon 10, which changes the nucleotide from Adenine to Thymine (A31483T), while in the second patient, we have identified an intronic change at g.35690A>G in Exon 10, which changes the nucleotide from Adenine to Guanine (A35690G) and in the third patient DNA sequence analysis identified an intronic change at g.35587A>G Exon 10, which changes the nucleotide from Adenine to Guanine (A35587G). Discussion and Conclusion: Although the partial loss of ATXN3 function may also contribute, the disease mechanism in MJD is believed to be a toxic gain-of-function. Several pathogenic cascades have been reported to be triggered by mutant ATXN3, but the critical molecular events driving MJD pathogenesis stay unresolved. While significant developments in studies have enhanced our knowledge of MJD, there is presently a lack of preventive treatment. Results presented here also expand our knowledge about MJD found in the eastern UP population.