Mutations in the potassium channel subunit KCNE1 are associated with early-onset familial atrial fibrillation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-12

AUTHORS

Morten S Olesen, Bo H Bentzen, Jonas B Nielsen, Annette B Steffensen, Jens-Peter David, Javad Jabbari, Henrik K Jensen, Stig Haunsø, Jesper H Svendsen, Nicole Schmitt

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutations in KV7.1, the pore-forming α-subunit of the IKs channel, have been associated with AF. We hypothesized that early-onset lone AF is associated with mutations in the IKs channel regulatory subunit KCNE1. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. More... »

PAGES

24

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2350-13-24

DOI

http://dx.doi.org/10.1186/1471-2350-13-24

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025334299

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22471742


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