title: Novel connexin40 missense mutations in patients with familial atrial fibrillation.
abstract: OBJECTIVE
  This research was aimed at screening connexin40, a cardiac gap junction protein alpha 5, for genetic defects in patients with familial atrial fibrillation (AF).
  
  
  METHODS
  The subjects included 218 unrelated families with lone AF and 200 ethnically matched unrelated healthy individuals as controls. The entire coding region of the connexin40 gene was sequenced initially in 218 unrelated probands with familial AF. The relatives of mutation carriers and 200 controls were subsequently genotyped for the presence of mutations identified in probands.
  
  
  RESULTS
  Three novel connexin40 mutations, p.V85I, p.L221I, and p.L229M, were identified in 3 of 218 unrelated AF families, respectively. These heterozygous missense mutations co-segregated with AF in the families and were absent in the 200 unrelated control subjects. A cross-species alignment of connexin40 protein sequences revealed that the altered amino acids were completely conserved evolutionarily.
  
  
  CONCLUSIONS
  The findings expand the spectrum of mutations in connexin40 linked to AF and provide new insight into the molecular aetiology involved in the pathogenesis of AF.
authors.affiliation: Department of Cardiovascular Research, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai 200030, China. yang99yang66@hotmail.com
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Xian-Ling
authors.initials: XL
authors.lastname: Zhang
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Wang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Tan
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Shi
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Jiang
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Fang
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001281:Atrial Fibrillation / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D002648:Child; D017630:Connexins / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D055815:Young Adult; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein