Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo, 160-8582, Japan.
J Hum Genet. 2018 Sep;63(9):989-996. doi: 10.1038/s10038-018-0479-y. Epub 2018 Jun 15.
Hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) present a high risk for sudden cardiac death in pediatric patients. The aim of this study was to identify disease-associated genetic variants in Japanese patients with pediatric HCM and RCM. We analyzed 67 cardiomyopathy-associated genes in 46 HCM and 7 RCM patients diagnosed before 16 years of age using a next-generation sequencing system. We found that 78% of HCM and 71% of RCM patients carried disease-associated genetic variants. Disease-associated genetic variants were identified in 80% of HCM patients with a family history and in 77% of HCM patients with no apparent family history (NFH). MYH7 and/or MYBPC3 variants comprised 76% of HCM-associated variants, whereas troponin complex-encoding genes comprised 75% of the RCM-associated variants. In addition, 91% of HCM patients with implantable cardioverter-defibrillators and infant cases had NFH, and the 88% of HCM patients carrying disease-associated genetic variants were males who carried MYH7 or MYBPC3 variants. Moreover, two disease-associated LAMP2, one DES and one FHOD3 variants, were identified in HCM patients. In this study, pediatric HCM and RCM patients were found to carry disease-associated genetic variants at a high rate. Most of the variants were in MYH7 or MYPBC3 for HCM and TNNT2 or TNNI3 for RCM.
肥厚型心肌病（HCM）和限制型心肌病（RCM）使儿科患者有发生心源性猝死的高风险。本研究旨在鉴定日本儿科 HCM 和 RCM 患者中的疾病相关遗传变异。我们使用下一代测序系统分析了 67 个与心肌病相关的基因，涉及 46 名 HCM 患者和 7 名 RCM 患者。结果发现，78%的 HCM 患者和 71%的 RCM 患者携带疾病相关的遗传变异。有家族史的 HCM 患者中有 80%、无明显家族史的 HCM 患者中有 77%（NFH）携带疾病相关的遗传变异。MYH7 和/或 MYBPC3 变异占 HCM 相关变异的 76%，而肌钙蛋白复合物编码基因占 RCM 相关变异的 75%。此外，91%携带植入式心脏复律除颤器的 HCM 患者和婴儿病例为 NFH，携带疾病相关遗传变异的 88%HCM 患者为男性，携带 MYH7 或 MYBPC3 变异。此外，还在 HCM 患者中鉴定出两种疾病相关的 LAMP2、一种 DES 和一种 FHOD3 变异。在这项研究中，发现儿科 HCM 和 RCM 患者携带疾病相关遗传变异的比例很高。大多数变异存在于 HCM 中的 MYH7 或 MYBPC3，以及 RCM 中的 TNNT2 或 TNNI3。
