A novel hemizygous SACS mutation identified by whole exome sequencing and SNP array analysis in a Chinese ARSACS patient

J Neurol Sci. 2016 Mar 15;362:111-4. doi: 10.1016/j.jns.2016.01.026. Epub 2016 Jan 18.

Abstract

The array of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has expanded worldwide after the first description in the Charlevoix-Saguenay region of Québec. Here, we report a Chinese ARSACS patient presenting progressive peripheral neuropathy (CMTNS2=15) with horizontal gaze nystagmus and mild spastic gait. Genetic studies including whole exome sequencing (WES), Sanger sequencing and single nucleotide polymorphism (SNP) array analysis revealed a novel hemizygous nonsense mutation (c.11803C>T, p.Gln3935X) of SACS and a 1.33Mb deletion involved in SACS on chromosome 13q12.12 in the patient. Our findings highlight the necessity of SACS mutation screening in the gene panel of inherited peripheral neuropathies, and stress the need of testing copy number variation (CNV) in SACS mutation screening.

Keywords: Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS); Deletion; Inherited peripheral neuropathy (IPN); Nonsense mutation.

Publication types

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

MeSH terms

  • Asian Continental Ancestry Group / genetics
  • Child
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Heat-Shock Proteins / genetics*
  • Humans
  • Muscle Spasticity / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Spinocerebellar Ataxias / congenital*
  • Spinocerebellar Ataxias / genetics

Substances

  • Heat-Shock Proteins
  • SACS protein, human

Supplementary concepts

  • Spastic ataxia Charlevoix-Saguenay type