Familial atrial fibrillation is a genetically heterogeneous disorder

Darbar, Dawood; Herron, Kathleen J.; Ballew, Jeffrey D.; Jahangir, Arshad; Gersh, Bernard J.; Shen, Win Kuang; Hammill, Stephen C.; Packer, Douglas L.; Olson, Timothy M.

doi:10.1016/s0735-1097(03)00465-0

Cited by 305 publications

(211 citation statements)

References 15 publications

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…The study subjects were clinically classified using a consistently applied set of definitions. 11,26 Briefly, 'lone AF' was defined as AF in individuals o60 years of age without hypertension or overt structural heart disease by clinical examination, ECG and echocardiography. 'Familial AF' was the lone AF in family members with X2 first-degree relatives with documented lone AF.…”

Section: Study Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation

et al. 2009

View full text Add to dashboard Cite

Accumulating evidence reveals that genetic variants play pivotal roles in familial atrial fibrillation (AF). However, the molecular defects in most patients with AF remain to be identified. Here, we report on three novel KCNA5 mutations that were identified in 4 of 120 unrelated AF families. Among them, T527M was found in two AF families, and A576V and E610K in two other AF families, respectively. The mutations T527M and A576V were also detected in 2 and 1 of 256 patients with idiopathic AF, respectively. The same mutations were not observed in 200 secondary AF patients and 500 controls. Functional analyses revealed consistent loss-of-function effects of mutant KCNA5 proteins on the ultrarapidly activating delayed rectifier potassium currents. These findings expand the spectrum of mutations in KCNA5 linked to AF and provide new insight into the molecular mechanism involved in AF.

show abstract

Section: Study Subjectsmentioning

confidence: 99%

“…25 Nevertheless, AF is a genetically heterogeneous disorder, and genetic defects in a significant proportion of AF patients remain to be identified. 26 In this study, we describe the identification and characterization of novel KCNA5 mutations as genetic determinants for AF.…”

Section: Introductionmentioning

confidence: 99%

Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation

et al. 2009

View full text Add to dashboard Cite

show abstract

“…6 A number of studies have demonstrated that AF and in particular lone AF have a substantial genetic component. [7][8][9][10][11][12][13] Oyen et al 14 have recently shown that an individual's risk of developing lone AF at a young age, increases drastically with both increasing number of relatives with lone AF and decreasing age at onset of the disease in these relatives, indicating an underlying genetic component in early onset lone AF.…”

Section: Introductionmentioning

confidence: 99%

Atrial fibrillation: the role of common and rare genetic variants

Olesen

Nielsen

Haunsø³

et al. 2013

Eur J Hum Genet

102

View full text Add to dashboard Cite

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1-2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized for many years. Presently, mutations in 25 genes have been associated with AF. However, the complexity of monogenic AF is illustrated by the recent finding that both gain-and loss-of-function mutations in the same gene can cause AF. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Following the first GWAS discovering the association between PITX2 and AF, several new GWAS reports have identified SNPs associated with susceptibility of AF. To date, nine SNPs have been associated with AF. The exact biological pathways involving these SNPs and the development of AF are now starting to be elucidated. Since the first GWAS, the number of papers concerning the genetic basis of AF has increased drastically and the majority of these papers are for the first time included in a review. In this review, we discuss the genetic basis of AF and the role of both common and rare genetic variants in the susceptibility of developing AF. Furthermore, all rare variants reported to be associated with AF were systematically searched for in the Exome Sequencing Project Exome Variant Server.

show abstract

“…Several studies suggest that up to one-third of all patients with AF have no obvious cause and are referred to as having lone AF (23,24). The absence of other causes associated with a high incidence of family history suggest the presence of a monogenic disease.…”

Section: Discussionmentioning

confidence: 99%