The Phenotypic Spectrum of a Mutation Hotspot Responsible for the Short QT Syndrome

JACC. Clinical Electrophysiology
Dan HuHector Barajas-Martinez

Abstract

This study sought to evaluate the phenotypic and functional expression of an apparent hotspot mutation associated with short QT syndrome (SQTS). SQTS is a rare channelopathy associated with a high risk of life-threatening arrhythmias and sudden cardiac death (SCD). Probands diagnosed with SQTS and their family members were evaluated clinically and genetically. KCNH2 wild-type (WT) and mutant genes were transiently expressed in HEK293 cells, and currents were recorded using whole-cell patch clamp and action potential (AP) clamp techniques. KCNH2-T618I was identified in 18 members of 7 unrelated families (10 men; median age: 24.0 years). All carriers showed 100% penetrance with variable expressivity. Eighteen members in 7 families had SCD. The average QTc intervals of probands and all carriers was 294.1 ± 23.8 ms and 313.2 ± 23.8 ms, respectively. Seven carriers received an implantable cardioverter-defibrillator. Quinidine with adequate plasma levels was effective in prolonging QTc intervals among 5 cases, but 3 cases still had premature ventricular contraction or nonsustained ventricular tachycardia. Bepridil successfully prevented drug-refractory ventricular fibrillation in 1 case with 19-ms prolongation of the QTc interval. Fu...Continue Reading

References

Feb 15, 2001·Cardiology·I GussakP Bjerregaard
Jul 31, 2003·Mutation Research·Igor B Rogozin, Youri I Pavlov
Aug 20, 2003·Circulation·Fiorenzo GaitaMartin Borggrefe
Dec 17, 2003·Circulation·Ramon BrugadaCharles Antzelevitch
Apr 20, 2004·Journal of the American College of Cardiology·Fiorenzo GaitaChristian Wolpert
May 26, 2004·Circulation·Chloé BellocqArthur A M Wilde
Nov 4, 2004·Journal of Molecular and Cellular Cardiology·Zhuoqian SunJun Zhou
Mar 12, 2005·Circulation Research·Silvia G PrioriJosé Jalife
Apr 15, 2005·Journal of Cardiovascular Electrophysiology·Kui HongRamon Brugada
Aug 20, 2005·Cardiovascular Research·Kui HongRamon Brugada
Aug 24, 2006·European Heart Journal·Carla GiustettoFiorenzo Gaita
Aug 22, 2007·Circulation·Christopher Newton-ChehChristopher J O'donnell
Feb 5, 2008·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Rainer SchimpfMartin Borggrefe
Aug 12, 2008·International Journal of Cardiology·Hideki ItohMinoru Horie
Oct 7, 2008·Pacing and Clinical Electrophysiology : PACE·Masahiro MizobuchiShigeru Nakamura
Nov 26, 2008·Progress in Biophysics and Molecular Biology·Mark J PerrinAdam P Hill
Mar 24, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Richard KobzaPaul Erne
Apr 25, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Sami Viskin
Mar 9, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Hiroshi WatanabeWataru Shimizu
Sep 8, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Elena BurashnikovCharles Antzelevitch
Dec 7, 2010·Journal of Molecular and Cellular Cardiology·Yaxun SunGan-Xin Yan
Feb 12, 2011·Journal of the American College of Cardiology·Michael H GollobJason D Roberts
Jul 30, 2011·Journal of the American College of Cardiology·Carla GiustettoFiorenzo Gaita
Feb 18, 2012·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Lia CrottiCharles Antzelevitch
Feb 5, 2013·Journal of the American College of Cardiology·Juan VillafañeMing-Lon Young
Sep 10, 2013·Journal of Electrocardiology·Charles Antzelevitch
Dec 3, 2013·Journal of the American College of Cardiology·Andrea MazzantiSilvia G Priori
Apr 25, 2014·Neurology·Amane ArakiGen Sobue
Sep 16, 2014·Circulation. Arrhythmia and Electrophysiology·Yoshiaki KanekoYoshifusa Aizawa
May 15, 2015·International Journal of Cardiology·Daniel Toshio HarrellNaomasa Makita
May 24, 2015·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Simone FreaFiorenzo Gaita

❮ Previous
Next ❯

Citations

May 1, 2019·Pacing and Clinical Electrophysiology : PACE·Yan HuangDan Hu
Apr 1, 2020·Cardiovascular Research·Lia CrottiMichael C Sanguinetti
Jul 19, 2019·Journal of Clinical Medicine·Oscar CampuzanoRamon Brugada
Nov 14, 2018·Frontiers in Cardiovascular Medicine·Oscar CampuzanoRamon Brugada
Feb 6, 2020·Frontiers in Genetics·Laura S RaschwitzMartin Borggrefe
Sep 14, 2021·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Xuehui FanIbrahim El-Battrawy

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

© 2022 Meta ULC. All rights reserved