ORPHA: 101016, 768; DO: 0110653;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20q11.21 | Long QT syndrome 12 | 612955 | Autosomal dominant | 3 | SNTA1 | 601017 |
A number sign (#) is used with this entry because of evidence that long QT syndrome-12 (LQT12) is caused by heterozygous mutation in the alpha-1 syntrophin gene (SNTA1; 601017) on chromosome 20q11.
Congenital long QT syndrome (LQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncope, seizure, or sudden death (Jongbloed et al., 1999).
For a discussion of genetic heterogeneity of long QT syndrome, see LQT1 (192500).
Ueda et al. (2008) analyzed the SNTA1 gene in 50 unrelated patients with long QT syndrome who were negative for mutations in the 11 known LQTS genes and identified a heterozygous missense mutation (A390V; 601017.0001) in 1 patient. This man, who had a corrected QT interval of 529 ms on electrocardiography (ECG), had been diagnosed with LQTS at 18 years of age after syncopal episodes but had no other symptoms of cardiac or skeletal muscle disease. The mutation was not found in 600 reference alleles.
In 39 unrelated patients with LQTS who were negative for mutation in 9 known LQT-associated genes, Wu et al. (2008) analyzed the candidate gene SNTA1 and identified a novel missense mutation (A257G; 601017.0002) in 2 women and 1 boy. The mutation was not detected in 400 ethnically matched control alleles. One of the women was ascertained after the sudden death of her 11-year-old son due to ventricular fibrillation; however, neither woman's parents had abnormalities on ECG and all parents were negative for mutation, consistent with de novo genetic change in the 2 women. The 17-year-old boy had congenital LQTS, with marked QT prolongation (550 ms) noted on ECG at 6 hours after birth. He experienced a syncopal episode at age 3 years and underwent Holter monitoring that confirmed prolongation of the QT interval but documented no arrhythmias. The patient's sister, mother, maternal uncle, and maternal grandmother also exhibited prolonged QT on ECG (460 ms to 530 ms), and the uncle, who had a history of syncope, died suddenly at age 25 during physical exertion. In addition to the SNTA1 missense mutation, affected members of this family also carried a variant of unknown significance in the KCNQ1 gene (607542), IVS7+5G-A.
Jongbloed, R. J. E., Wilde, A. A. M., Geelen, J. L. M. C., Doevendans, P., Schaap, C., Van Langen, I., van Tintelen, J. P., Cobben, J. M., Beaufort-Krol, G. C. M., Geraedts, J. P. M., Smeets, H. J. M. Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum. Mutat. 13: 301-310, 1999. [PubMed: 10220144] [Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)13:4<301::AID-HUMU7>3.0.CO;2-V]
Ueda, K., Valdivia, C., Medeiros-Domingo, A., Tester, D. J., Vatta, M., Farrugia, G., Ackerman, M. J., Makielski, J. C. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc. Nat. Acad. Sci. 105: 9355-9360, 2008. [PubMed: 18591664] [Full Text: https://doi.org/10.1073/pnas.0801294105]
Wu, G., Ai, T., Kim, J. J., Mohapatra, B., Xi, Y., Li, Z., Abbasi, A., Purevjav, E., Samani, K., Ackerman, M. J., Qi, M., Moss, A. J., Shimizu, W., Towbin, J. A., Cheng, J., Vatta, M. Alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circ. Arrhythm. Electrophysiol. 1: 193-201, 2008. [PubMed: 19684871] [Full Text: https://doi.org/10.1161/CIRCEP.108.769224]