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

M I Shadrina; M V Shulskaya; S A Klyushnikov; T Nikopensius; M Nelis; P A Kivistik; A A Komar; S A Limborska; S N Illarioshkin; P A Slominsky

doi:10.1186/s40673-016-0040-8

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

Cerebellum Ataxias. 2016 Jan 13:3:2. doi: 10.1186/s40673-016-0040-8. eCollection 2016.

Authors

Affiliations

¹ Institute of Molecular Genetics RAS, Moscow, Russia.
² Department of Neurogenetics, Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
³ Estonian Genome Centre, University of Tartu, Tartu, Estonia.
⁴ Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115 USA.

Abstract

Background: Spinocerebellar ataxias (SСAs) 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 four-generation family with autosomal dominant (AD) non-progressive SCA with mild symptoms was conducted. The genotyping of this family revealed no frequent pathogenic mutations. So the objective of this study was to identify the 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 structure prediction, 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.

Keywords: ITPR1; Sanger sequencing; Spinocerebellar ataxia; Whole-exome sequencing.