Shan Lishen, Makita Naomasa, Xing Yanlin, Watanabe Sayake, Futatani Takeshi, Ye Fei, Saito Kazuyoshi, Ibuki Keijiro, Watanabe Kazuhiro, Hirono Keiichi, Uese Keiichiro, Ichida Fukiko, Miyawaki Toshio, Origasa Hideki, Bowles Neil E, Towbin Jeffrey A
Department of Pediatrics, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Mol Genet Metab. 2008 Apr;93(4):468-74. doi: 10.1016/j.ymgme.2007.10.009.
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.
左心室心肌致密化不全（LVNC）是一种基因异质性疾病。人类心脏钠通道α亚基基因（SCN5A）的突变参与了心律失常和心肌病的病理生理过程。本研究旨在比较伴有或不伴有心律失常的LVNC患者中SCN5A变异体的频率，并探讨变异体与疾病严重程度之间的关系。从62例日本LVNC先证者的外周血中分离DNA，其中包括17例家族性病例和45例散发性病例。使用单链构象多态性分析（SSCP）和DNA测序对血样进行SCN5A变异体筛查。在7例家族性病例和12例散发性病例中鉴定出7种变异体，分别为rs6599230:G＞A、c.453C＞T、c.1141-3C＞A、rs1805124:A＞G（p.H558R）、rs1805125:C＞T（p.P1090L）、c.3996C＞T和rs1805126:T＞C。伴有心律失常的患者中SCN5A变异体的频率显著高于不伴有心律失常的患者（50%对7%：P = 0.0003），提示这些变异体是心律失常的危险因素，并支持编码离子通道的基因参与LVNC病理生理过程的假说。伴有心力衰竭的LVNC患者中SCN5A变异体的发生率也较高，提示SCN5A变异体和/或心律失常的存在会增加LVNC的严重程度。
