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.
PATIENTS AND 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.
CONCLUSION: 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.