title: Two distinct clinical features and cognitive impairment in amyotrophic lateral sclerosis patients with TARDBP gene mutations in the Chinese population.
abstract: Mutations in the TARDBP gene have been identified as a major causative factor in amyotrophic lateral sclerosis (ALS). However, few reports have analyzed the relationship of genotype-phenotype, especially in Chinese ALS patients. Our study investigated the presence and frequency of TARDBP mutations in Chinese patients with ALS. Additionally, we investigated correlations among clinical features and TARDBP gene mutations in a large ALS family with the p.M337 V mutation and one sporadic ALS (SALS) patient with the p.S393 L mutation. The pedigree with the p.M337 V mutation showed variable clinical features with a long lifespan, particularly cognitive impairment. One patient carrying the p.S393 L mutation experienced ALS with cognitive impairment; the patient also had a family history of frontotemporal dementia (FTD). This is the first report of detailed genetic and clinical characterizations of the TARDBP gene in a Chinese population. This research is also the first to demonstrate that the p.M337 V and the p.S393 L mutations are related to cognitive impairment in ALS patients. The mutation frequency of TARDBP was 5.6% in Chinese, SOD1-negative familial ALS (FALS), which was much higher than that reported in previous studies conducted with Caucasian populations, whereas the TARDBP mutation frequency was lower in the Chinese population with regard to SALS patients. Our results emphasize the importance of the genetic and clinical characterization of TARDBP mutations in ALS, which allows us to understand the genotype-phenotype relationship and relative frequencies in different populations.
authors.affiliation: Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.
authors.forename: XiaoDong
authors.initials: X
authors.lastname: Ju
authors.affiliation: Medical Research Center, Peking University Third Hospital, Beijing, China.
authors.forename: WenChao
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: XiaoGang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Neurology, Peking University Third Hospital, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Medical Research Center, Peking University Third Hospital, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Medical Research Center, Peking University Third Hospital, Beijing, China. Electronic address: dengmin1706@gmail.com.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications* / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D000072105:Superoxide Dismutase-1; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C000606290:SOD1 protein, human; C000598624:TARDBP protein, human; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Clinical phenotype; Cognitive impairment; Genotype; TARDBP gene mutation