ITPR1 gene p.Val1553Met mutation in Russian family with mild Spinocerebellar ataxia

Abstract

Background: Spinocerebellar ataxias (S?As) are a highly heterogeneous group of inherited neurological disorders.The symptoms of ataxia vary in individual patients and even within the same SCA subtype. A study of a fourgenerationfamily with autosomal dominant (AD) non-progressive SCA with mild symptoms was conducted. Thegenotyping of this family revealed no frequent pathogenic mutations. So the objective of this study was to identifythe genetic causes of the disease in this family with the technology of whole-exome sequencing (WES).Methods and results: WES, candidate variant analysis with further Sanger sequencing, mRNA secondary structureprediction, and RSCU analysis were performed; a heterozygous missense mutation in ITPR1 was identified.Conclusion: Our study confirms the fact that ITPR1 gene plays a certain role in the pathogenesis of SCAs, and,therefore, we suggest that c.4657G>A p.Val1553Met) is a disease-causing mutation in the family studied.