ORPHA: 334; DO: 0050650;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12p12.1 | ?Atrial fibrillation, familial, 12 | 614050 | Autosomal dominant | 3 | ABCC9 | 601439 |
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-12 (ATFB12) is caused by heterozygous mutation in the ABCC9 gene (601439) on chromosome 12p12. One such patient has been reported.
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).
Olson et al. (2007) studied a 53-year-old white woman who presented with a 10-year history of daily paroxysms of atrial fibrillation (AF) that peaked with morning activity. At the time of presentation, the episodes were increasing in frequency and associated with near syncope. Myocardial, valvular, and coronary artery disease were excluded by echocardiography and cardiac perfusion stress testing; ventricular wall thickness and atrial volume were normal. Electrophysiologic analysis identified a focal source of rapidly firing electrical activity within the vein of Marshall, which initiated AF under adrenergic provocation. The patient's AF was refractory to antiarrhythmic medical management, but was eliminated after electrical isolation of the vein of Marshall; she remained in sinus rhythm and symptom free over a 2.5-year follow-up period.
In a 53-year-old white woman with paroxysmal AF, Olson et al. (2007) sequenced cardiac ion channel genes and identified a heterozygous missense mutation in the ABCC9 gene (T1547I; 601439.0003) that was not found in 2,000 unrelated and predominantly white controls. The patient's first-degree relatives declined to undergo clinical or genetic testing. Targeted screening for the T1547I ABCC9 mutation in an additional 154 patients with diverse presentations of AF indicated that this specific genetic substitution is not common.
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]
Olson, T. M., Alekseev, A. E., Moreau, C., Liu, X. K., Zingman, L. V., Miki, T., Seino, S., Asirvatham, S. J., Jahangir, A., Terzic, A. K(ATP) channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation. Nat. Clin. Pract. Cardiovasc. Med. 4: 110-116, 2007. [PubMed: 17245405] [Full Text: https://doi.org/10.1038/ncpcardio0792]