KCNE3 mutation V17M identified in a patient with lone atrial fibrillation.
BACKGROUND
Atrial fibrillation (AF) is the most common cardiac rhythm disorder with a lifetime risk for development of 25% for people aged 40 or older. In this study we aim for the functional assessment of a mutation in KCNE3 identified in a proband with early-onset lone AF.


METHODS
Screening of genomic DNA from the proband led to identification of a KCNE3 V17M missense mutation. We heterologously expressed the accessory channel subunit in Xenopus laevis oocytes together with its known interacting potassium channel alpha-subunits. Further, we applied RT-PCR on human total RNA from left and right atria and ventricle.


RESULTS
Electrophysiological recordings revealed an increased activity of Kv4.3/KCNE3 and Kv11.1/KCNE3 generated currents by the mutation, thereby conferring susceptibility of mutation carriers to faster cardiac action potential repolarization and thus vulnerability to re-entrant wavelets in the atria and thereby AF.


CONCLUSIONS
Here we report a novel mutation in KCNE3 identified in a proband with early-onset lone AF possibly leading to gain-of-function of several cardiac currents. We suggest abnormalities in the KCNE3 gene as a potential genetic risk factor for initiation and/or maintenance of AF.
Lundby
Alicia
A
The Danish National Research Foundation Centre for Cardiac Arrhythmia, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
Ravn
Lasse Steen
LS
Svendsen
Jesper Hastrup
JH
Hauns
Stig
S
Olesen
Søren-Peter
SP
Schmitt
Nicole
N
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001281:Atrial Fibrillation / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D015640:Ion Channel Gating; D008297:Male; D008715:Methionine / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000235:genetics*; D014633:Valine / Q000235:genetics*
C418492:KCNE3 protein, human; D024642:Potassium Channels, Voltage-Gated; D008715:Methionine; D014633:Valine