Congenital long QT syndrome 12 (LQT12)

Congenital long QT syndrome 12 (LQT12)

Congenital long QT syndrome 12 (LQT12): Congenital long QT syndrome 12 (LQTS 12) is caused by a mutation in the gene coding for alpha-1 syntrophin gene (SNTA1) [1]. The mutation was identified by evaluating a person with a QTC of 530 msec and negative for the 11 known LQTS susceptibility genes (LQT 1-11). A missense mutation A390V-SNTA1 was found in this person with recurrent syncope. He was diagnosed to have LQTS at the age of 18 years after a syncopal episode. SNTA1 links nNOS (neuronal nitric oxide synthase) to the nNOS inhibitor plasma membrane Ca-ATPase subtype 4b (PMCA4b). SNTA1  is also associated with SCN5A (cardiac sodium channel). This mutation causes an increase in the late sodium current in the myocardial cells. NOS blockers could partially inhibit the increase in late sodium current.

OMIM database has designated this gene (SNTA1) as LQTS 12 (LQT12) associated gene. The gene is located on chromosome 20q11.21 [2].

Reference

1. Kazuo Ueda, Carmen Valdivia, Argelia Medeiros-Domingo, David J Tester, Matteo Vatta, Gianrico Farrugia, Michael J Ackerman, Jonathan C Makielski. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9355-60.
2. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {601017}: {9/22/2015}: . World Wide Web URL: https://omim.org/