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

L Liu; X B Li; X H Zi; L Shen; Zh M Hu; Sh X Huang; D L Yu; H B Li; K Xia; B S Tang; R X Zhang

doi:10.1016/j.jns.2016.01.026

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.

Authors

L Liu¹, X B Li¹, X H Zi¹, L Shen², Zh M Hu³, Sh X Huang¹, D L Yu⁴, H B Li⁵, K Xia³, B S Tang⁶, R X Zhang⁷

Affiliations

¹ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
² Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
³ National Key Lab of Medical Genetics, Central South University, Changsha 410078, Hunan Province, China.
⁴ Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
⁵ Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
⁶ Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; National Key Lab of Medical Genetics, Central South University, Changsha 410078, Hunan Province, China.
⁷ Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China. Electronic address: zhangruxu@vip.163.com.

PMID: 26944128
DOI: 10.1016/j.jns.2016.01.026

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 People / 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