ORPHA: 334; DO: 0050650;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.11 | Atrial fibrillation, familial, 13 | 615377 | Autosomal dominant | 3 | SCN1B | 600235 |
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-13 (ATFB13) is caused by heterozygous mutation in the SCN1B gene (600235) on chromosome 19q13.
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 women with atrial fibrillation and a mutation in the SCN1B gene (see MOLECULAR GENETICS). One was a 68-year-old white woman with paroxysmal atrial fibrillation (AF) and moderate aortic stenosis. She was diagnosed at 58 years of age, and electrocardiogram (ECG) showed saddleback-type ST segment elevation in leads V1 to V3 that was present both during AF and during sinus rhythm, with beat-to-beat and day-to-day variability. Echocardiography revealed left atrial enlargement. No family members had documented AF, but her grandmother and daughter had a history of stroke. The other patient was a 57-year-old black woman with paroxysmal lone AF, which was diagnosed at 35 years of age. Her ECG was normal and did not show ST segment elevation or any conduction abnormality. Echocardiography revealed left atrial enlargement. At 54 years of age, she developed episodic paroxysmal AF with rapid ventricular response that was unresponsive to medication, and she underwent atrioventricular nodal ablation followed by dual-chamber pacemaker implantation. There was no family history of AF, although her mother had hypertension and a pacemaker. Neither patient had a history of ventricular tachyarrhythmias or syncope.
Watanabe et al. (2009) screened the 4 genes encoding sodium channel beta subunits, SCN1B, SCN2B (601327), 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 female patients, 1 with AF and aortic stenosis and 1 with lone AF, who had heterozygous missense mutations in the SCN1B gene, R85H (600235.0006) and D153N (600235.0007), respectively. Sequencing the SCN5A gene (600163) in the 2 women revealed no mutations, and the SCN1B variants were not found in a total of 638 controls. Another 2 patients were found to have mutations in the SCN2B gene (601327.0001 and 601327.0002; see ATFB14, 615378), 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]