%0 Journal Article
%T Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation
%A Morten S Olesen
%A Bo H Bentzen
%A Jonas B Nielsen
%A Annette B Steffensen
%A Jens-Peter David
%A Javad Jabbari
%A Henrik K Jensen
%A Stig Hauns£¿
%A Jesper H Svendsen
%A Nicole Schmitt
%J BMC Medical Genetics
%D 2012
%I BioMed Central
%R 10.1186/1471-2350-13-24
%X In 209 unrelated early-onset lone AF patients (< 40 years) the entire coding sequence of KCNE1 was bidirectionally sequenced. We analyzed the identified KCNE1 mutants electrophysiologically in heterologous expression systems.Two non-synonymous mutations G25V and G60D were found in KCNE1 that were not present in the control group (n = 432 alleles) and that have not previously been reported in any publicly available databases or in the exom variant server holding exom data from more than 10.000 alleles. Proband 1 (female, age 45, G25V) had onset of paroxysmal AF at the age of 39 years. Proband 2 (G60D) was diagnosed with lone AF at the age of 33 years. The patient has inherited the mutation from his mother, who also has AF. Both probands had no mutations in genes previously associated with AF. In heterologous expression systems, both mutants showed significant gain-of-function for IKs both with respect to steady-state current levels, kinetic parameters, and heart rate-dependent modulation.Mutations in KV7.1 leading to gain-of-function of IKs current have previously been described in lone AF, yet this is the first time a mutation in the beta-subunit KCNE1 is associated with the disease. This finding further supports the hypothesis that increased potassium current enhances AF susceptibility.Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. It is responsible for considerable morbidity and mortality, and its population prevalence has reached epidemic proportions, affecting almost seven million patients in the European Union and the USA combined [1-4].In most cases AF is associated with cardiac risk factors such as hypertensive, ischemic, and/or structural heart disease [1,5]. However, 10-20% of patients suffering from AF are younger than 60 years of age and lack the traditional risk factors for AF. These patients are considered as having "lone" AF [2]. The mechanisms underlying AF are not fully understood, but a heterogeneous model based on the
%K Lone AF
%K Genetics
%K KV7.1
%K KCNE1
%K IKs current
%U http://www.biomedcentral.com/1471-2350/13/24