title: Prevalence and spectrum of GJA5 mutations associated with lone atrial             fibrillation.
abstract: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia observed             in clinical practice and a major contributor to cardiovascular morbidity and mortality.             Accumulating evidence indicates a substantial genetic basis for AF. However, AF             is genetically heterogeneous and the hereditary components responsible for AF             remain to be identified in the majority of patients. The cardiac gap junction             protein α 5 (GJA5) is specifically expressed in atrial myocytes and is associated             with the coordinated electrical activation of the atria, providing a rationale             to screen GJA5 as a logical candidate gene for AF. A cohort of 310 unrelated patients             with lone AF and their available relatives were included in this study. A group             of 200 unrelated healthy individuals matched for age, gender and race were also             included as controls. The entire coding region and splice sites of the GJA5 gene             were initially sequenced in 310 unrelated AF patients. The relatives of mutation             carriers and 200 controls were subsequently genotyped for the presence of identified             mutations. As a result, 4 novel heterozygous GJA5 mutations, p.K107R, p.L223M,             p.Q236H and p.I257L, were identified in 4 of 310 unrelated AF patients, respectively,             with a prevalence of ~1.29%. Genetic analysis of the carriers' families showed             that in each family the missense mutation was present in all the affected family             members. Absent in the 400 reference alleles, these mutations altered the amino             acids highly conserved among various species, with the exception of p.I257L. In             conclusion, this study expands the spectrum of GJA5 mutations associated with             AF and provides novel insights into the molecular basis of AF, suggesting potential             implications for the improved, gene-specific rhythm control strategies.
authors.affiliation: Department of Cardiology, Beijing Hospital, Beijing 100730, PR China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Shi
authors.forename: Jie-Fu
authors.initials: JF
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ruo-Gu
authors.initials: RG
authors.lastname: Li
authors.forename: Ying-Jia
authors.initials: YJ
authors.lastname: Xu
authors.forename: Xin-Kai
authors.initials: XK
authors.lastname: Qu
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Fang
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Yi-Qing
authors.initials: YQ
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D055815:Young Adult; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein