Novel connexin40 missense mutations in patients with familial atrial fibrillation.
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.
Yang
Yi-Qing
YQ
Department of Cardiovascular Research, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, 241 West Huaihai Road, Shanghai 200030, China. yang99yang66@hotmail.com
Liu
Xu
X
Zhang
Xian-Ling
XL
Wang
Xin-Hua
XH
Tan
Hong-Wei
HW
Shi
Hai-Feng
HF
Jiang
Wei-Feng
WF
Fang
Wei-Yi
WY
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
D017630:Connexins; D000097003:Gap Junction alpha-5 Protein