Mutations of the SCN4B-encoded sodium channel beta4 subunit in familial atrial fibrillation.
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Li RG, Wang Q, Xu YJ, Zhang M, Qu XK, Liu X, Fang WY, Yang YQ
Mutations of the SCN4B-encoded sodium channel beta4 subunit in familial atrial fibrillation.
Int J Mol Med. 2013 Jul;32(1):144-50. doi: 10.3892/ijmm.2013.1355. Epub 2013 Apr 22.
- PubMed ID
- 23604097 [ View in PubMed]
- Abstract
Atrial fibrillation (AF) represents the most common form of sustained cardiac arrhythmia and accounts for substantial morbidity and mortality. Mutations in the cardiac sodium channel alpha, beta1, beta2 and beta3 subunit genes (SCN5A, SCN1B, SCN2B and SCN3B) have been associated with AF, which suggests that mutations in the sodium channel beta4 subunit gene, SCN4B, are also involved in the pathogenesis of AF. To examine this hypothesis, the coding exons and exon-intron boundaries of SCN4B were sequenced in 170 unrelated index patients with familial AF. The available relatives of the probands carrying the identified mutations and 200 unrelated ethnically matched healthy individuals used as the controls were subsequently genotyped. The pathogenic potential of a SCN4B sequence variation was predicted using MutationTaster. As a result, 2 novel heterozygous SCN4B mutations, p.V162G and p.I166L, were identified in 2 unrelated families with AF transmitted in an autosomal dominant pattern, respectively. In each family the mutation co-segregated with AF and was absent in the 400 control chromosomes. The mutations altered the amino acids evolutionarily highly conserved across species and were both predicted to be disease-causing. To the best of our knowledge, this is the first study to demonstrate an association of SCN4B mutations with AF, suggesting SCN4B as a novel AF susceptibility gene.