CACNA1B gene variants in adult-onset isolated focal dystonia

Neurol Sci. 2021 Mar;42(3):1113-1117. doi: 10.1007/s10072-020-04778-8. Epub 2020 Oct 13.

Abstract

Background: Isolated focal dystonia (IFD) is a heterogeneous group of potentially invalidating movement disorders. The etiopathogenesis is complex, both genetic and environmental factors playing a role, but remains elusive. The CACNA1B gene codes for the N-type neuronal voltage-gated calcium channels CaV2.2, which may play a role in the development of some IFD.

Methods: We analyzed samples from the GENDYS cohort for mutations in CACNA1B gene, using targeted next-generation sequencing (NGS).

Results: The GENDYS cohort consists of 120 people with adult-onset IFD (cervical dystonia 47.5%, blepharospasm 47.2%, others 8.3%). Of these, 35% had subsequent topographical extension. Average age at onset was 42 and average disease durations 8 years. Targeted NGS revealed a novel frameshift mutation c.2291AGG > A, in exon 19, and a previously reported variant, c.6834T > G, in exon 47.

Conclusion: Our findings suggest that disease-causing mutations in CACNA1B gene may be involved in the development of some adult-onset IFD. To our knowledge, this is the first study that identified a disease-causing CACNA1B gene mutation in association with adult-onset IFD.

Keywords: CACNA1B gene; Disease-causing variants; Isolated focal dystonia; Next-generation sequencing.

MeSH terms

  • Adult
  • Blepharospasm*
  • Calcium Channels, N-Type / genetics
  • Dystonic Disorders* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation / genetics

Substances

  • CACNA1B protein, human
  • Calcium Channels, N-Type