Novel SACS mutations identified by whole exome sequencing in a norwegian family with autosomal recessive spastic ataxia of Charlevoix-Saguenay

PLoS One. 2013 Jun 13;8(6):e66145. doi: 10.1371/journal.pone.0066145. Print 2013.


We employed whole exome sequencing to investigate three Norwegian siblings with an autosomal recessive spastic ataxia and epilepsy. All patients were compound heterozygous (c.13352T>C, p.Leu4451Pro; c.6890T>G, p.Leu2297Trp) for mutations in the SACS gene establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The clinical features shown by our patients were typical of this disorder with the exception of epilepsy, which is a rare manifestation. This is the first report of ARSACS in Scandinavian patients and our findings expand the genetic and clinical spectrum of this rare disorder. Moreover, we show that exome sequencing is a powerful and cost-effective tool for the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Brain / pathology
  • Exome
  • Family
  • Female
  • Genes, Recessive*
  • Heat-Shock Proteins / genetics*
  • Heterozygote
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Muscle Spasticity / diagnosis
  • Muscle Spasticity / genetics*
  • Mutation*
  • Norway
  • Sequence Alignment
  • Spinocerebellar Ataxias / congenital*
  • Spinocerebellar Ataxias / diagnosis
  • Spinocerebellar Ataxias / genetics


  • Heat-Shock Proteins
  • SACS protein, human

Supplementary concepts

  • Spastic ataxia Charlevoix-Saguenay type

Grant support

This work was supported by grants from the Western Norway Health Trust, University of Bergen. Western Norway Regional Health Authority (Helse Vest). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.