title: SCN5A mutation in Chinese patients with arrhythmogenic right ventricular dysplasia.
abstract: BACKGROUND
  Arrhythmogenic right ventricular dysplasia (ARVD) is a genetically determined disorder, characterized by two components: cardiomyopathy and arrhythmia. To date, the ion channel-related pathogenesis underlying this phenomenon has been poorly understood. The aim of this study was to systematically evaluate the sodium channel variants in Chinese patients with ARVD.
  
  
  METHODS
  Patients meeting the diagnostic guidelines of ARVD revised in 2010 were enrolled. All exons and exon-intron boundaries of the SCN5A gene and desmosomal genes known to be associated with ARVD, including DSC2, DSG2, DSP, JUP, and PKP2, were sequenced by direct DNA sequencing. A total of 12 unrelated index patients were included in the study.
  
  
  RESULTS
  Eight of the patients developed ventricular tachycardia (VT) and ventricular fibrillation (VF), one of them showed epsilon wave, one of them showed type-1 Brugada wave, seven of them exhibited syncope or dizziness, and none of the patients had a family history of SCD. A new missense heterozygote mutation, I137M, in SCN5A was found in proband 5 with recurrent palpitations and a high incidence of VT. I137M is in exon 4 of SCN5A, at the S1 segment in domain I of Nav1.5, which predicted a substitution of isoleucine for methionine at codon site 137 (p. Ile137Met, I137M). I137M was not detected in 400 healthy control chromosomes from individuals of the same ethnic background, which indicated that this mutation was a conservative site in the SCN5A gene, and the encoded protein Nav1.5 might have a functional defect resulting in arrhythmia.
  
  
  CONCLUSIONS
  This was the first study to systematically investigate sodium channel variants in Chinese patients with ARVD; a new SCN5A mutation, I137M, was found. This finding may provide new evidence of the genetic pathogenesis of ARVD in Chinese patients, implying that the SCN5A gene should be screened in patients with ARVD and VT/VF.
authors: The Cardiology Department, The Second Affiliated Hospital of NanChang University, 330006, Jiangxi, China.
authors: J
authors: J
authors: Yu
authors: J
authors: J
authors: Hu
authors: X
authors: X
authors: Dai
authors: Q
authors: Q
authors: Cao
authors: Q
authors: Q
authors: Xiong
authors: X
authors: X
authors: Liu
authors: X
authors: X
authors: Liu
authors: Y
authors: Y
authors: Shen
authors: Q
authors: Q
authors: Chen
authors: W
authors: W
authors: Hua
authors: K
authors: K
authors: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics*; D002681:China; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human