ORPHA: 334; DO: 0050650;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q24.3 | Atrial fibrillation, familial, 9 | 613980 | Autosomal dominant | 3 | KCNJ2 | 600681 |
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-9 (ATFB9) is caused by heterozygous mutation in the KCNJ2 gene (600681) on chromosome 17q24.
Atrial fibrillation (AF) 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 atrial fibrillation, see 608583.
Xia et al. (2005) studied a 4-generation Chinese family segregating autosomal dominant atrial fibrillation. The proband was a 59-year-old man who had been diagnosed with AF at 54 years of age and had paroxysmal AF 2 to 3 times a month. His father and an older sister, who were diagnosed at age 58 years and 50 years, respectively, had persistent atrial fibrillation before their deaths. A younger sister, who was diagnosed at 50 years of age, had paroxysmal AF as frequently as once or twice a week, and a 57-year-old niece was diagnosed with paroxysmal AF on 24-hour electrocardiographic (ECG) recordings. All affected members of the family had normal QT intervals on ECG, experienced no episodes of muscle weakness or syncope, and did not have frequent premature ventricular contractions or ventricular tachycardia on 24-hour ECG monitoring. Serum potassium levels were within normal limits. None of the patients exhibited any syndromic features such as cleft palate, low-set ears, short stature, clinodactyly, syndactyly, or brachydactyly.
In the 4-generation Chinese family with atrial fibrillation, Xia et al. (2005) performed linkage analysis and obtained a 2-point lod score of 1.93 (theta = 0.0) for the flanking microsatellite marker D17S949.
In the probands from 30 unrelated Chinese kindreds with atrial fibrillation (AF), Xia et al. (2005) analyzed 10 candidate ion channel or transporter-related genes, and identified a heterozygous missense mutation in the KCNJ2 gene (600681.0014) in 1 of the probands. All affected individuals in this 4-generation family carried the mutation, as well as the 42- and 33-year-old nephews of the proband, in whom AF was not detected on 24-hour ECG monitoring. In view of their relatively young age and the paroxysmal nature of AF, Xia et al. (2005) did not exclude that the nephews were affected.
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]
Xia, M., Jin, Q., Bendahhou, S., He, Y., Larroque, M.-M., Chen, Y., Zhou, Q., Yang, Y., Liu, Y., Liu, B., Zhu, Q., Zhou, Y., and 12 others. A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem. Biophys. Res. Commun. 332: 1012-1019, 2005. [PubMed: 15922306] [Full Text: https://doi.org/10.1016/j.bbrc.2005.05.054]