ORPHA: 334; DO: 0050650;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11q23.3 | Atrial fibrillation, familial, 14 | 615378 | Autosomal dominant | 3 | SCN2B | 601327 |
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-14 (ATFB14) is caused by heterozygous mutation in the SCN2B gene (601327) on chromosome 11q23.
Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997).
For a discussion of genetic heterogeneity of familial atrial fibrillation, see ATFB1 (608583).
Watanabe et al. (2009) described 2 unrelated men with atrial fibrillation and a mutation in the SCN2B gene (see MOLECULAR GENETICS). One was a 61-year-old white man who had paroxysmal atrial fibrillation (AF) and hypertension. He was diagnosed with AF at 55 years of age, and electrocardiogram (ECG) showed saddleback-type ST segment elevation in the right precordial leads during sinus rhythm, with a prolonged PR interval of 220 ms. The magnitude of ST segment elevation showed day-to-day variability. Echocardiography was normal. He had no family history of AF. The other patient was a 57-year-old white man with paroxysmal lone AF, who had saddleback-type ST segment elevation in the right precordial leads and slight left atrial enlargement on echocardiography. Both his father and mother had AF, as well as coronary artery disease.
Watanabe et al. (2009) screened the 4 genes encoding sodium channel beta subunits, SCN1B (600235), SCN2B, SCN3B (608214), and SCN4B (608256), in 480 patients with atrial fibrillation, including 118 patients with lone AF and 362 patients with AF and other cardiovascular disease. They identified 2 unrelated male patients, 1 with AF and hypertension and 1 with lone AF, who had heterozygous missense mutations in the SCN2B gene, R28W (601327.0001) and R28Q (601327.0002), respectively. Sequencing of the SCN5A gene (600163) in the 2 men revealed no mutations, and the SCN2B variants were not found in a total of 638 controls. Another 2 patients were found to have mutations in the SCN1B gene (600235.0006 and 600235.0007; see ATFB13, 615377), but no disease-causing mutations were identified in SCN3B or SCN4B.
Brugada, R., Tapscott, T., Czernuszewicz, G. Z., Marian, A. J., Iglesias, A., Mont, L., Brugada, J., Girona, J., Domingo, A., Bachinski, L. L., Roberts, R. Identification of a genetic locus for familial atrial fibrillation. New Eng. J. Med. 336: 905-911, 1997. [PubMed: 9070470] [Full Text: https://doi.org/10.1056/NEJM199703273361302]
Watanabe, H., Darbar, D., Kaiser, D. W., Jiramongkolchai, K., Chopra, S., Donahue, B. S., Kannankeril, P. J., Roden, D. M. Mutations in sodium channel beta-1- and beta-2-subunits associated with atrial fibrillation. Circ. Arrhythm. Electrophysiol. 2: 268-278, 2009. [PubMed: 19808477] [Full Text: https://doi.org/10.1161/CIRCEP.108.779181]