title: A novel missense mutation of TNNI2 in a Chinese family cause distal arthrogryposis type 1.
abstract: The distal arthrogryposis (DA) syndromes are a group of disorders characterized by congenital contractures of limbs. According to phenotypical characteristics, DA syndromes have been clinically classified into 10 types. Currently, at least nine disease causing genes have been identified for different types of DA. Here, we report a 3-generation Chinese pedigree with three DA affected members. We performed whole exome sequencing on two affected and one unaffected individuals of this family and successfully identified a novel missense mutation in TNNI2 as the pathogenic mutation. The TNNI2 gene encodes a subunit of the troponin complex, a contractile machinery of the muscle. The mutation p.F178C that could change the H-bond formation of a neighboring residue occurs at a highly conserved position, suggesting that this variation probably affects the TNNI2 protein function. Our study also demonstrates the power of whole exome sequencing in causal mutation identification for phenotypically variable and genetically heterogeneous disorders.
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Haiou
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pediatric Orthopedic, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000595:Amino Acid Sequence; D001176:Arthrogryposis / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D019210:Troponin I / Q000737:chemistry / Q000235:genetics*
chemical_list: C518658:TNNI2 protein, human; D019210:Troponin I
keywords: TNNI2; distal arthrogryposis; mutation; whole exome sequencing