Short QT Syndrome and Atrial Fibrillation Caused by Mutation in KCNH2

Abstract

Our study confirms that N588K is a hotspot for familial form of the short QT syndrome. The disease is clinically heterogeneous, as indicated by the fact that, in the three families with the same mutation, there is a wide range of symptoms, varying from atrial to ventricular fibrillation and sudden death. While the implantation of a defibrillator appears warranted due to the inducibility at PES, the clinical follow-up provides indication that the class Ic agent propafenone could be effective to prevent episodes of paroxysmal atrial fibrillation.

Prevalence of early-onset atrial fibrillation in congenital long QT syndrome

“…In 2003, Chen et al 5 reported a family with early-onset AF that had a gainof-function mutation in the KCNQ1-encoded potassium channel. A second gain-of-function mutation in KCNQ1 associated with AF and a short QT interval was reported in 2005 by Hong et al 6 Gain-of-function mutations in KCNH2-encoded potassium channels, 7 loss-offunction mutations in the atrial-specific KCNA5-encoded Kv1.5 potassium channel, 8 and loss-of-function mutations in the SCN5A-encoded sodium channel 9 have been reported recently in familial AF.…”

A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation

“…Genome-wide linkage analysis with polymorphic genetic markers mapped multiple susceptibility loci for AF on human chromosomes 10q22, 6q14-16, 11p15.5, 5p13, 10p11-q21 and 5p15, of which AF-causing mutations in 2 genes, KCNQ1 on chromosome 11p15.5 and NUP155 on chromosome 5p13, were identified and functionally characterized (15)(16)(17)(18)(19)(20)(21). Additionally, a genetic scan of candidate genes revealed a long list of AF associated genes, including KCNE2, KCNE3, KCNE5, KCNH2, KCNJ2, KCNA5, SCN5A, SCN1B, SCN2B, SCN3B, NPPA, GJA1 and GJA5 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Nevertheless, AF is a genetically heterogeneous disease and the genetic determinants for AF in a large proportion of patients remain unclear.…”

Connexin40 nonsense mutation in familial atrial fibrillation

“…While the structural heart diseases or systemic disorders, such as coronary artery disease, rheumatic heart disease, cardiomyopathy, congenital heart defects, pericarditis, congestive heart failure, hypertension, hyperthyroidism, and electrolyte imbalance, predispose to AF (4), AF also occurs in individuals without any known risk factors and growing evidence points to a genetic basis for the pathogenesis of AF (5)(6)(7)(8)(9)(10)(11)(12)(13). Furthermore, several chromosomal loci linked to AF have been mapped and AF-related mutations in multiple genes, including the connexin40 encoding cardiac gap junction membrane channel protein ·5, have been identified (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). However, AF is a genetically heterogeneous disorder and the molecular basis of AF remains unknown in the majority of cases (27).…”