title: Whole exome sequencing identifies a novel missense FBN2 mutation co-segregating in a four-generation Chinese family with congenital contractural arachnodactyly.
abstract: BACKGROUND
  Congenital contractural arachnodactyly (CCA) is an autosomal dominant rare genetic disease, estimated to be less than 1 in 10,000 worldwide. People with this condition often have permanently bent joints (contractures), like bent fingers and toes (camptodactyly).
  
  
  METHODS
  In this study, we investigated the genetic aetiology of CCA in a four-generation Chinese family. The blood samples were collected from 22 living members of the family in the Yangquan County, Shanxi Province, China. Of those, eight individuals across 3 generations have CCA. Whole exome sequencing (WES) identified a missense mutation involving a T-to-G transition at position 3229 (c.3229 T > G) in exon 25 of the FBN2 gene, resulting in a Cys 1077 to Gly change (p.C1077G). This previously unreported mutation was found in all 8 affected individuals, but absent in 14 unaffected family members. SIFT/PolyPhen prediction and protein conservation analysis suggest that this novel mutation is pathogenic. Our study extended causative mutation spectrum of FBN2 gene in CCA patients.
  
  
  CONCLUSIONS
  This study has identified a novel missense mutation in FBN2 gene (p.C1077G) resulting in CCA in a family of China.
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Xingping
authors.initials: X
authors.lastname: Guo
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China. 16398656@qq.com.
authors.forename: Chunying
authors.initials: C
authors.lastname: Song
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Meng
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Qinzhao
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Xue
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yu
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Huaixiu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanxi Key Laboratory of Birth Defects and Cell Regeneration, Shanxi Population and Family Planning Research Institute, 11 Beiyuan Street, Taiyuan, Shanxi, 030006, People's Republic of China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, 90095, USA. xinminli@mednet.ucla.edu.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Li
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D054119:Arachnodactyly / Q000175:diagnosis / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D003286:Contracture / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004252:DNA Mutational Analysis; D000071840:Fibrillin-2 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: D000071840:Fibrillin-2; D004247:DNA
keywords: Congenital contractural arachnodactyly; FBN2; Mutation; Whole exome sequencing