A novel subclinical missense mutation (L1825P) in the SCN5A gene was identified in a patient with cisapride-induced long-QT syndrome, demonstrating both gain- and loss-of-function features.
Case Report (n=1)
BACKGROUND: Subclinical mutations in genes associated with the congenital long-QT syndromes (LQTS) have been suggested as a risk factor for drug-induced LQTS and accompanying life-threatening arrhythmias. Recent studies have identified genetic variants of the cardiac K+ channel genes predisposing affected individuals to acquired LQTS. We have identified a novel Na+ channel mutation in an individual who exhibited drug-induced LQTS. METHODS AND RESULTS: An elderly Japanese woman with documented QT prolongation and torsade de pointes during treatment with the prokinetic drug cisapride underwent mutational analysis of LQTS-related genes. A novel missense mutation (L1825P) was identified within the C-terminus region of the cardiac Na+ channel (SCN5A). The L1825P channel heterologously expressed in tsA-201 cells showed Na+ current with slow decay and a prominent tetrodotoxin-sensitive noninactivating component, similar to the gain-of-function phenotype most commonly observed for SCN5A-associated congenital LQTS (LQT3). In addition, L1825P exhibited loss of function Na+ channel features characteristic of Brugada syndrome. Peak Na+ current density observed in cells expressing L1825P was significantly diminished, and the voltage dependence of activation and inactivation was shifted toward more positive and negative potentials, respectively. CONCLUSIONS: This study demonstrates that subclinical mutations in the LQTS-related gene SCN5A may predispose certain individuals to drug-induced cardiac arrhythmias.
Makita et al. (Tue,) conducted a case report in Drug-induced long-QT syndrome (n=1). Cisapride was evaluated on Identification and functional characterization of genetic mutation. A novel subclinical missense mutation (L1825P) in the SCN5A gene was identified in a patient with cisapride-induced long-QT syndrome, demonstrating both gain- and loss-of-function features.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: