title: A novel hemizygous SACS mutation identified by whole exome sequencing and SNP array analysis in a Chinese ARSACS patient.
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.
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
authors.forename: X B
authors.initials: XB
authors.lastname: Li
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Zi
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: L
authors.initials: L
authors.lastname: Shen
authors.affiliation: National Key Lab of Medical Genetics, Central South University, Changsha 410078, Hunan Province, China.
authors.forename: Zh M
authors.initials: ZhM
authors.lastname: Hu
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
authors.forename: Sh X
authors.initials: ShX
authors.lastname: Huang
authors.affiliation: Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
authors.forename: D L
authors.initials: DL
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China.
authors.forename: H B
authors.initials: HB
authors.lastname: Li
authors.affiliation: National Key Lab of Medical Genetics, Central South University, Changsha 410078, Hunan Province, China.
authors.forename: K
authors.initials: K
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: B S
authors.initials: BS
authors.lastname: Tang
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China. Electronic address: zhangruxu@vip.163.com.
authors.forename: R X
authors.initials: RX
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D009128:Muscle Spasticity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000151:congenital* / Q000235:genetics
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human
keywords: Autosomal recessive spastic ataxia of Charlevoix–Saguenay (ARSACS); Deletion; Inherited peripheral neuropathy (IPN); Nonsense mutation