Other entities represented in this entry:
ORPHA: 130, 334; DO: 0110224;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11q24.1 | Brugada syndrome 7 | 613120 | Autosomal dominant | 3 | SCN3B | 608214 |
| 11q24.1 | Atrial fibrillation, familial, 16 | 613120 | Autosomal dominant | 3 | SCN3B | 608214 |
A number sign (#) is used with this entry because of evidence that Brugada syndrome-7 (BRGDA7) and atrial fibrillation-16 (ATFB16) are caused by heterozygous mutation in the SCN3B gene (608214) on chromosome 11q24.
Brugada Syndrome 7
Brugada syndrome is characterized by an ST segment elevation in the right precordial electrocardiogram leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts. The syndrome typically manifests during adulthood, with a mean age of sudden death of 41 +/- 15 years, but also occurs in infants and children (summary by Antzelevitch et al., 2005).
For a discussion of genetic heterogeneity of Brugada syndrome, see BRGDA1 (601144).
Atrial Fibrillation 16
Atrial fibrillation (AF) is the most common cardiac arrhythmia in the clinical setting, with a prevalence of 1% in the general population; prevalence increases with age and reaches more than 8% in the ninth decade of life. AF accounts for more than 15% of strokes, and is associated with worsening heart failure and increased mortality. More than 30% of cases of AF are considered to be 'lone AF,' unassociated with coronary artery disease, hypertension, valvular heart disease, hyperthyroidism, heart failure, or structural heart disease (summary by Wang et al., 2010).
For a discussion of genetic heterogeneity of atrial fibrillation, see ATFB1 (608583).
Brugada Syndrome 7
Hu et al. (2009) studied an asymptomatic 64-year-old Caucasian man of German, Swedish, and Native American ancestry who presented with a resting electrocardiogram (ECG) showing slight ST segment elevation and negative T waves in V1, which was suggestive of Brugada syndrome. Type 1 ST segment elevation, diagnostic of Brugada syndrome, was unmasked in leads V1 and V2 after sodium channel blockade with procainamide. An internal cardioverter defibrillator (ICD) was implanted; interrogation of the ICD 3 years later revealed an episode of atrial flutter with 2:1 atrioventricular block. Family history was negative for sudden cardiac death, although the proband had 2 paternal aunts and 3 paternal uncles who all died of lung cancer.
Atrial Fibrillation 16
Olesen et al. (2011) reported 3 unrelated Danish patients with early-onset lone atrial fibrillation (AF) and mutation in the SCN3B gene (see MOLECULAR GENETICS). At 39 years of age, the first patient had onset of AF that eventually became persistent AF. His deceased mother and aunt had permanent AF late in life. The patient was highly symptomatic, and had undergone 12 DC conversions as well as 3 radiofrequency ablation procedures. Flecainide testing did not induce a Brugada-like ECG pattern. The second patient had onset of AF at 35 years of age, and had persistent AF. There was no family history of AF, but his mother had premature atrial complexes on ECG. This patient did not consent to a flecainide test. The third patient had onset of AF at 36 years of age, and had paroxysmal AF. There was no family history of AF; Holter monitoring showed a large number of premature ventricular complexes. The patient was not available for flecainide testing.
Brugada Syndrome 7
In a 64-year-old man with Brugada syndrome, who was negative for mutation in 9 'Brugada-susceptibility' genes, Hu et al. (2009) identified heterozygosity for a missense mutation in the SCN3B gene (608214.0001). The mutation was not found in the proband's unaffected brother or in 360 Caucasian, 120 Turkish, and 112 Sephardic Jewish reference alleles.
Atrial Fibrillation 16
Wang et al. (2010) sequenced the SCN3B gene in 477 patients with atrial fibrillation (AF) from the GeneID Han Chinese population, and identified 1 patient with lone AF who was heterozygous for a missense mutation (A130V; 608214.0003). The mutation was absent from 500 ethnically matched controls.
Olesen et al. (2011) analyzed the SCN3B and SCN4B (608256) genes in 192 unrelated Danish patients with onset of lone AF before 40 years of age, and identified 3 missense mutations in SCN3B (see, e.g., 608214.0004 and 608214.0005), including an L10P substitution (608214.0001) that had previously been found in a patient with Brugada syndrome. No mutations were found in SCN4B. The 3 mutation-positive patients were screened for mutations in 10 known AF-associated genes; a missense variant in the SCN5A gene that did not appear to be pathogenic was detected in 1 of the patients (see 608214.0004). A flecainide test performed in 1 of the patients did not induce a Brugada-like ECG pattern.
Antzelevitch, C., Brugada, P., Borggrefe, M., Brugada, J., Brugada, R., Corrado, D., Gussak, I., LeMarec, H., Nademanee, K., Perez Riera, A. R., Shimizu, W., Schulze-Bahr, E., Tan, H., Wilde, A. Brugada syndrome: report of the second consensus conference. Circulation 111: 659-670, 2005. Note: Erratum: Circulation 112: e74, 2005. [PubMed: 15655131] [Full Text: https://doi.org/10.1161/01.CIR.0000152479.54298.51]
Hu, D., Barajas-Martinez, H., Burashnikov, E., Springer, M., Wu, Y., Varro, A., Pfeiffer, R., Koopmann, T. T., Cordeiro, J. M., Guerchicoff, A., Pollevick, G. D., Antzelevitch, C. A mutation in the beta-3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ. Cardiovasc. Genet. 2: 270-278, 2009. [PubMed: 20031595] [Full Text: https://doi.org/10.1161/CIRCGENETICS.108.829192]
Olesen, M. S., Jespersen, T., Nielsen, J. B., Liang, B., Moller, D. V., Hedley, P., Christiansen, M., Varro, A., Olesen, S.-P., Haunso, S., Schmitt, N., Svendsen, J. H. Mutations in sodium channel beta-subunit SCN3B are associated with early-onset lone atrial fibrillation. Cardiovasc. Res. 89: 786-793, 2011. [PubMed: 21051419] [Full Text: https://doi.org/10.1093/cvr/cvq348]
Wang, P., Yang, Q., Wu, X., Yang, Y., Shi, L., Wang, C., Wu, G., Xia, Y., Yang, B., Zhang, R., Xu, C., Cheng, X., Li, S., Zhao, Y., Fu, F., Liao, Y., Fang, F., Chen, Q., Tu, X., Wang, Q. K. Functional dominant-negative mutation of sodium channel subunit gene SCN3B associated with atrial fibrillation in a Chinese GeneID population. Biochem. Biophys. Res. Commun. 398: 98-104, 2010. [PubMed: 20558140] [Full Text: https://doi.org/10.1016/j.bbrc.2010.06.042]