SCN5A variants in Japanese patients with left ventricular  noncompaction and arrhythmia.
Left ventricular noncompaction (LVNC) is a genetically heterogenous disorder. Mutations in the human cardiac sodium channel alpha-subunit gene (SCN5A) are involved in the pathophysiology of cardiac arrhythmias and cardiomyopathies. This study was performed to compare the frequency of SCN5A variants in LVNC patients with or without arrhythmias, and to investigate the relationship between variants and disease severity. DNA was isolated from the peripheral blood of 62 Japanese probands with LVNC, comprising 17 familial cases and 45 sporadic cases. Blood samples were screened for variants in SCN5A using single-strand conformational polymorphism analysis (SSCP) and DNA sequencing. Seven variants, rs6599230:G > A, c.453C > T, c.1141-3C > A, rs1805124:A > G (p.H558R), rs1805125:C > T (p.P1090L), c.3996C > T, and rs1805126:T > C were identified in 7 familial and 12 sporadic cases. The frequency of SCN5A variants was significantly higher in the patients with arrhythmias than those without (50% vs 7%: P = 0.0003), suggesting these variants represent a risk factor for arrhythmia and supporting the hypothesis that genes encoding ion channels are involved in LVNC pathophysiology. The LVNC patients with heart failure also had high occurrence of SCN5A variants, suggesting the presence of SCN5A variants and/or arrhythmias increase the severity of LVNC.
Shan
Lishen
L
Department of Pediatrics, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Makita
Naomasa
N
Xing
Yanlin
Y
Watanabe
Sayake
S
Futatani
Takeshi
T
Ye
Fei
F
Saito
Kazuyoshi
K
Ibuki
Keijiro
K
Watanabe
Kazuhiro
K
Hirono
Keiichi
K
Uese
Keiichiro
K
Ichida
Fukiko
F
Miyawaki
Toshio
T
Origasa
Hideki
H
Bowles
Neil E
NE
Towbin
Jeffrey A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006333:Heart Failure / Q000235:genetics; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000235:genetics*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels