title: Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis.
abstract: BACKGROUND
  TARDBP mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim is to investigate the association between TARDBP mutations and Chinese patients with ALS.
  
  
  METHODS
  71 SALS patients and 5 FALS families with non-SOD1 mutations were screened for TARDBP mutations via direct sequencing.
  
  
  RESULTS
  A novel heterozygous variation, Ser292Asn (875G>A), was identified in the proband and 4 asymptomatic relatives including the children of the dead patient from a FALS family. Thus the dead patient, the proband's brother, was speculated to carry Ser292Asn though his sample was unavailable to the detection. This variation was not found in 200 unrelated control subjects. A homology search of the TDP-43 protein in different species demonstrated that it was highly conserved. Also, it was predicted to be deleterious to protein function with SIFT-calculated probabilities of 0.00. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (Gly40Gly and Ala366Ala) and one novel polymorphism (239-18t>c).
  
  
  CONCLUSIONS
  The present data have extended the spectrum of TARDBP mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients.
authors.affiliation: Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, PR China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Xiong
authors.forename: Jin-Yang
authors.initials: JY
authors.lastname: Wang
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Sun
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Qiao
authors.forename: Qiao-Juan
authors.initials: QJ
authors.lastname: Zheng
authors.forename: Gui-Xian
authors.initials: GX
authors.lastname: Zhao
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002681:China; D002878:Chromosomes, Human, Pair 1; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D004268:DNA-Binding Proteins