title: Arrhythmogenic cardiomyopathy in a patient with a rare loss-of-function KCNQ1 mutation.
abstract: BACKGROUND
  Ventricular tachycardia (VT) is a common manifestation of advanced cardiomyopathies. In a subset of patients with dilated cardiomyopathy, VT is the initial and the cardinal manifestation of the disease. The molecular genetic basis of this subset of dilated cardiomyopathy is largely unknown.
  
  
  RESULTS
  We identified 10 patients with dilated cardiomyopathy who presented with VT and sequenced 14 common causal genes for cardiomyopathies and arrhythmias. Functional studies included cellular patch clamp, confocal microscopy, and immunoblotting. We identified nonsynonymous variants in 4 patients, including a rare missense p.R397Q mutation in the KCNQ1 gene in a 60-year-old man who presented with incessant VT and had mild cardiac dysfunction. The p.R397Q mutation was absent in an ethnically matched control group, affected a conserved amino acid, and was predicted by multiple algorithms to be pathogenic. Co-expression of the mutant KCNQ1 with its partner unit KCNE1 was associated with reduced tail current density of slowly activating delayed rectifier K(+) current (IKs). The mutation reduced membrane localization of the protein.
  
  
  CONCLUSIONS
  Dilated cardiomyopathy with an initial presentation of VT may be a forme fruste of arrhythmogenic cardiomyopathy caused by mutations in genes encoding the ion channels. The findings implicate KCNQ1 as a possible causal gene for arrhythmogenic cardiomyopathy.
authors.affiliation: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.X., Q.Z., Y.S., J.Y., S.Y., K.H.).
authors.forename: Qinmei
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: The Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.C., J.X., R.W., K.H.).
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.X., Q.Z., Y.S., J.Y., S.Y., K.H.).
authors.forename: Qiongqiong
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.C., J.X., R.W., K.H.).
authors.forename: Jinyan
authors.initials: J
authors.lastname: Xie
authors.affiliation: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.X., Q.Z., Y.S., J.Y., S.Y., K.H.).
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: The Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.C., J.X., R.W., K.H.).
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.affiliation: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.X., Q.Z., Y.S., J.Y., S.Y., K.H.).
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.X., Q.Z., Y.S., J.Y., S.Y., K.H.).
authors.forename: Sujuan
authors.initials: S
authors.lastname: Yan
authors.affiliation: Center for Cardiovascular Genetics at The University of Texas Health Science Center-Houston and Texas Heart Institute, Houston, TX (A.J.M.).
authors.forename: Ali J
authors.initials: AJ
authors.lastname: Marian
authors.affiliation: Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.X., Q.Z., Y.S., J.Y., S.Y., K.H.) The Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China (Q.C., J.X., R.W., K.H.).
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis / Q000235:genetics; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D004562:Electrocardiography / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D035583:Rare Diseases; D012016:Reference Values; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human
keywords: KCNQ1; arrhythmias; cardiomyopathy; genetics; mutation; ventricular tachycardia