title: Identification of C9orf72 repeat expansions in patients with amyotrophic lateral sclerosis and frontotemporal dementia in mainland China.
abstract: The GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in white populations. To estimate the frequency of hexanucleotide repeats in patients with ALS and FTD from mainland China, we screened for C9orf72 in a cohort of 128 patients and 150 control subjects using the repeat-primed polymerase chain reaction method. We observed pathogenic repeat expansions in a family with ALS-FTD and in a patient with sporadic FTD. In the family with ALS-FTD, the proband and the 2 asymptomatic siblings exhibited C9orf72 repeat expansions, and the clinical feature of the proband was characterized by pure motor syndrome with no cognitive impairment. The patient with sporadic FTD presented primarily with deteriorating behavior and mental status. Genotype analysis revealed that the proband shared the previously reported 20-single nucleotide polymorphism risk haplotype, whereas the patient with sporadic FTD carried all single nucleotide polymorphisms except rs2814707-A. To our knowledge, this study is the first to report 2 C9orf72 mutation patients in mainland China, and they shared the similar risk haplotype identified in white populations, suggesting that ALS and FTD associated with C9orf72 mutation was probably derived from a single founder.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiao
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; State Key Laboratory of Medical Genetics, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Beisha
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; State Key Laboratory of Medical Genetics, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; State Key Laboratory of Medical Genetics, Changsha 410008, China; Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha 410008, China. Electronic address: shenlu2505@126.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*; D012306:Risk
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: Amyotrophic lateral sclerosis; C9orf72; Frontotemporal dementia; Hexanucleotide repeats; Risk haplotype