Screening of mutations in GNAL in sporadic dystonia patients

Mov Disord. 2014 Aug;29(9):1193-6. doi: 10.1002/mds.25794. Epub 2014 Jan 9.

Abstract

Background: GNAL mutations have been shown to cause adult-onset isolated dystonia, a disabling movement disorder characterized by involuntary muscle contractions causing twisting and repetitive movements or abnormal postures.

Methods: To test the frequency of GNAL mutations in a series of 137 German patients with sporadic dystonia patients we used next-generation sequencing of amplicon-derived barcoded NexteraXT libraries for the coding exons and adjacent intronic sequences of GNAL.

Results: In our cohort we identified 1 pathogenic nonsense mutation (c.733C>T, p.R245*) in a patient with cervical dystonia. In a second patient a synonymous coding nonsynonymous variant (c.G252A, p.E84E) was detected, which is predicted to alter a splice site.

Conclusions: Our findings further support GNAL as causative gene in adult-onset isolated dystonia.

Keywords: GNAL; isolated dystonia; mutation; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis Regulatory Proteins / genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA-Binding Proteins / genetics
  • Dystonic Disorders / genetics*
  • Female
  • GTP-Binding Protein alpha Subunits / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Nuclear Proteins / genetics
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • GTP-Binding Protein alpha Subunits
  • Nuclear Proteins
  • THAP1 protein, human
  • olfactory G protein subunit alpha olf