title: Connexin40 nonsense mutation in familial atrial fibrillation.
abstract: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with substantial morbidity and mortality. Genetic variants play important roles in the pathogenesis of AF. However, AF is a genetically heterogeneous disorder, and the genetic determinants in most patients with AF remain to be identified. In this study, the entire coding region of the connexin40 gene, encoding the cardiac gap junction membrane channel protein alpha5, was sequenced in 126 unrelated probands with familial AF. A novel heterozygous mutation, c.145C<T, in connexin40, was identified in a proband. The mutation was predicted to introduce a premature stop codon at amino acid position 49 (p.Q49X). This nonsense mutation was present in all the living relatives of the mutation carrier, co-segregating with AF in the family with a penetrance of 100%. However, it was absent in 200 ethnically matched unrelated control individuals. The findings suggest a pathogenic link between the compromised connexin40 function and familial AF, hence providing new insight into the molecular mechanisms involved in AF.
authors.affiliation: Department of Cardiovasular Research, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai, P.R. China. yang99yang66@hotmail.com
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
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
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D001281:Atrial Fibrillation / Q000235:genetics*; D018389:Codon, Nonsense; D017630:Connexins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018389:Codon, Nonsense; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein