Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons of the brain, brainstem and spinal cord. To date, mutations in more than 30 genes have been linked to the pathogenesis of ALS. Among them, SOD1, FUS and TARDBP are ranked as the three most common genes associated with ALS. However, no mutation analysis has been reported in central-southern China. In this study, we sequenced SOD1, FUS and TARDBP in a central-southern Chinese cohort of 173 patients with ALS (15 familial ALS and 158 sporadic ALS) to detect mutations. As a result, five missense mutations in SOD1, namely, p.D101N, p.D101G, p.C111Y, p.N86S and p.V87A, were identified in three unrelated familial probands and three sporadic cases; two mutations in FUS were found in two unrelated familial probands, including an insertion mutation (p.P525_Y526insY) and a missense mutation (p.R521H); no variants of TARDBP were observed in patients. Therefore, SOD1 mutations were present in 20.0% of familial ALS patients and 1.9% of sporadic ALS patients, while FUS mutations were responsible for 13.3% of familial ALS cases, and TARDBP mutations were rare in either familial or sporadic ALS cases. This study broadens the known mutational spectrum in patients with ALS and further demonstrates the necessity for genetic screening in ALS patients from central-southern China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Lihua
L
Hou
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Bin
B
Jiao
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Tingting
T
Xiao
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Lu
L
Zhou
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Zhifan
Z
Zhou
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Juan
J
Du
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Xinxiang
X
Yan
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.
Junling
J
Wang
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.|State Key Laboratory of Medical Genetics, Changsha 410008, China.
Beisha
B
Tang
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.|Hunan Province Key Laboratory in Neurodegenerative Disorders, Central South University, Changsha 410008, China.|State Key Laboratory of Medical Genetics, Changsha 410008, China.
Lu
L
Shen
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002681:China; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
D004268:DNA-Binding Proteins; C000599550:FUS protein, human; D034702:RNA-Binding Protein FUS; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; D000072105:Superoxide Dismutase-1