Key result
A novel KCNE3 V17M missense mutation identified in a proband with early-onset lone atrial fibrillation increased Kv4.3/KCNE3 and Kv11.1/KCNE3 currents, suggesting a gain-of-function mechanism.
Case Report (n=1)
The KCNE3 V17M mutation leads to a gain-of-function in cardiac potassium currents, suggesting it as a potential genetic risk factor for early-onset lone atrial fibrillation.
No change to AF management warranted; hypothesis-generating for KCNE3 in early-onset lone AF.
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. CONCLUSION: 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.
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Lundby et al. (2008) conducted a case report in Early-onset lone atrial fibrillation (n=1). KCNE3 V17M missense mutation was evaluated on Electrophysiological activity of Kv4.3/KCNE3 and Kv11.1/KCNE3 generated currents. A novel KCNE3 V17M missense mutation identified in a proband with early-onset lone atrial fibrillation increased Kv4.3/KCNE3 and Kv11.1/KCNE3 currents, suggesting a gain-of-function mechanism.
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