title: ITPR1 gene p.Val1553Met mutation in Russian family with mild Spinocerebellar ataxia.
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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Molecular Genetics RAS, Moscow, Russia.
authors.forename: M I
authors.initials: MI
authors.lastname: Shadrina
authors.affiliation: Institute of Molecular Genetics RAS, Moscow, Russia.
authors.forename: M V
authors.identifier: 0000-0003-1274-2901
authors.initials: MV
authors.lastname: Shulskaya
authors.affiliation: Department of Neurogenetics, Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: S A
authors.initials: SA
authors.lastname: Klyushnikov
authors.affiliation: Estonian Genome Centre, University of Tartu, Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Nikopensius
authors.affiliation: Estonian Genome Centre, University of Tartu, Tartu, Estonia.
authors.forename: M
authors.initials: M
authors.lastname: Nelis
authors.affiliation: Estonian Genome Centre, University of Tartu, Tartu, Estonia.
authors.forename: P A
authors.initials: PA
authors.lastname: Kivistik
authors.affiliation: Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, OH 44115 USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Komar
authors.affiliation: Institute of Molecular Genetics RAS, Moscow, Russia.
authors.forename: S A
authors.initials: SA
authors.lastname: Limborska
authors.affiliation: Department of Neurogenetics, Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: S N
authors.initials: SN
authors.lastname: Illarioshkin
authors.affiliation: Institute of Molecular Genetics RAS, Moscow, Russia.
authors.forename: P A
authors.initials: PA
authors.lastname: Slominsky
keywords: ITPR1; Sanger sequencing; Spinocerebellar ataxia; Whole-exome sequencing