You are here

Article Text

Article menu
Download PDFPDF
Online mutation report
The common SCN5A mutation R1193Q causes LQTS-type electrophysiological alterations of the cardiac sodium channel
  1. Q Wang1,
  2. S Chen1,
  3. Q Chen1,2,
  4. X Wan3,
  5. J Shen4,
  6. G A Hoeltge5,
  7. A A Timur1,
  8. M T Keating6,
  9. G E Kirsch3,7
  1. 1Department of Molecular Cardiology, Lerner Research Institute, and Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
  2. 2Cole Eye Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
  3. 3Department of Physiology and Biophysics, Case Western Reserve University MetroHealth Campus, Cleveland, OH 44109, USA
  4. 4University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA
  5. 5Department of Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
  6. 6Department of Cell Biology and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
  7. 7ChanTest Inc, and Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44128, USA
  1. Correspondence to:
 Dr Q Wang
 Director, Center for Cardiovascular Genetics, ND4-38, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44190, USA; wangq2ccf.org or Dr G E Kirsch, ChanTest Inc, 14656 Neo Parkway, Cleveland, Ohio 44128, USA; gkirschchantest.com

https://doi.org/10.1136/jmg.2003.013300

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Long QT syndrome (LQTS) is a prototypic arrhythmic disorder that is characterised by prolonged QT interval (or QTc) on electrocardiograms (ECGs), syncope, and sudden death from episodic ventricular tachyarrhythmias, specifically torsade de pointes.1–4 LQTS causes sudden deaths in young, otherwise healthy, individuals, and in many cases the first symptom is sudden death. Both genetic and acquired factors contribute to the pathogenesis of LQTS. Predisposing genetic mutations have been identified in six genes. These include the cardiac potassium channel genes KvLQT1 or KCNQ1 (chromosome 11p15.5, LQT1),5–7HERG or KCNH2 (7q35–36, LQT2),8KCNE1 (21q22, LQT5),9,10 and KCNE2 (21q22, LQT6),11 the cardiac sodium channel gene SCN5A (3p21–24, LQT3),12,13 and the non-ion channel ankyrin-B gene encoding a protein that links ion channels to the cytoskeleton (4q25–27, LQT4).14

    Acquired long QT syndrome (aLQTS) is LQTS caused by factors such as bradycardia, cardiac ischaemia, metabolic abnormalities (including hypocalaemia and hypomagnesaemia), starvation (anorexia nervosa), and various medical manipulations and medications including general anaesthetics, antibiotics, antihistamines, and ironically anti-arrhythmic agents.15,16 Acquired LQTS is common, with a population prevalence rate of up to 8%.17 Because almost all cases of acquired LQTS are sporadic, genetic analysis of acquired LQTS has been lagging behind inherited LQTS. However, there has recently been increased interest in determining the genetic basis of acquired LQTS by studying genes causing inherited LQTS.18–21 We carried out a similar analysis in this study.

    Voltage gated sodium channels are transmembrane proteins responsible for generating cardiac action potentials, and for rapid conduction of electrical signals through cardiac tissues. The cardiac sodium channel is a large protein of 2016 amino acids encoded by the SCN5A gene.22 The cardiac sodium channel consists of a pore forming α-subunit composed of four homologous domains (I–IV), each containing …

    View Full Text

    Footnotes

    • Conflicts of interest: none declared