Analysis of gene mutations encoding sarcomeric proteins in sudden death cases caused by cardiomyopathy
Analysis of gene mutations encoding sarcomeric proteins in sudden death cases caused by cardiomyopathy
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发表时间：
2014-03
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通讯作者：
C. Murakami;Shigeki Nakamura;Kazuho Maeda;Wataru Irie;Momoko Oishi;Chizuko Sasaki;Naomi Nakamaru
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作者：
C. Murakami;Shigeki Nakamura;Kazuho Maeda;Wataru Irie;Momoko Oishi;Chizuko Sasaki;Naomi Nakamaru
目的：对经尸检确诊为心肌病（CM）的病例进行了编码肌节蛋白的7个基因的综合筛选，并探讨了通过筛选这些基因进行遗传学诊断的可能性。研究方法：收集37例CMs所致心源性猝死患者的血液和左心室标本，并以200例血液标本作为对照。设计了覆盖所有编码外显子的引物。采用聚合酶链反应（PCR）扩增DNA，用ABI 3130型遗传分析仪直接测序。结果：仅在CM病例中检测到22个突变，其中包括4个新突变。还检测到48个单核苷酸多态性（SNPs）。肥厚型心肌病（HCM）与对照组、扩张型心肌病（DCM）与对照组之间的等位基因频率差异有统计学意义，TNT 2中c.68-5delC和c.348C>T，TNNI 3中c.258T>A，MYBPC 3中c.1927+ 89 C>G。提示至少有3个SNPs（c.68-5delC、c.348C>T和c.25- 8 T>A）和2个SNPs（c.348C>T和c.1927+ 89 C>G）分别对HCM和DCM的基因诊断有重要意义。结论：我们的数据清楚地表明，编码肌节蛋白的致病基因的遗传分析有助于决定法医尸检病例中CM的诊断，并有助于防止其家族中CM引起的进一步死亡。
Objective: Comprehensive screening for 7 genes encoding sarcomeric proteins were performed in consented autopsy cases diagnosed as cardiomyopathies (CMs), and the possibility of the genetic based diagnosis by screening for these genes was also examined. Methods: Blood samples and left ventricular samples were obtained from 37 sudden cardiac death cases caused by CMs and 200 blood samples were used as controls. Primers covering all coding exons were designed. DNA samples were amplified by polymerase chain reaction (PCR), and PCR products were sequenced by direct sequencing with the ABI 3130 genetic analyzer. Results: Twenty-two mutations were detected in only the CM cases, including 4 new mutations. Forty-eight single nucleotide polymorphisms (SNPs) were also detected. Significant differences in allele frequencies between hypertrophic cardiomyopathy (HCM) and controls, and dilated cardiomyopathy (DCM) and controls were found in c.68-5delC and c.348 C>T in TNNT2, and c.258T>A in TNNI3 and c.1927+89C>G in MYBPC3, respectively. It was indicated that at least 3 SNPs (c.68-5delC, c.348C>T and c.25-8T>A) and 2 SNPs (c.348C>T and c.1927+89C>G) were important to genetic based diagnosis of HCM and DCM, respectively. Conclusions: Our data clearly suggested that genetic analysis of disease causing genes encoding sarcomeric proteins was useful to decide the diagnosis of CMs for forensic autopsy cases and to help prevent further deaths caused by CMs in their families.