PDF(Pubmed)
Abstract：
Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500-1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. MYH7 gene encoding a myosin heavy chain beta, together with MYPBC3 gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of MYH7 responsible for HCM in a five-generation family with a history of cardiac problems. Methods: The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance. Genetic analysis was performed using next-generation-sequencing and Sanger method. Results: The medical history of the presented family began with a prenatal diagnosis of HCM in the first child of a family with previously healthy parents. Five generations of the family had a long history of sudden cardiac death and cardiac problems. A NM_000257.4:c.2342T>A (p.Leu781Gln) variant was detected in the MYH7 gene. It was heterozygous in the proband and in all affected individuals in a large family. The variant was present in 10 affected members of the family, and was absent in 7 members. The clinical course of the disease was severe in several members of the family: three family members died of sudden cardiac death, one patient required heart transplantation, three underwent septal myectomy, and three required implantable cardioverter defibrillator (ICD) implantation. Conclusion: Herein, we report a MYH7 variant responsible for HCM. Familial HCM is inherited primarily in autosomal dominant mode, which is in accordance with our study. However, the presented family showed a broad clinical spectrum of HCM. Out of 10 family members with positive genetic testing 8 had severe presentation of the disease and 2 had a mild phenotype. This suggests that the severity of the disease may depend on other factors, most likely genetic.
摘要：
背景：肥厚型心肌病（HCM）是一种遗传性疾病，患病率为1：500-1：3000。编码肌节蛋白的基因中的变异体是该疾病的主要原因。MYH7基因编码肌球蛋白重链β，与MYPBC3基因一起是两个最常受影响的基因。这种疾病的临床表现在个体之间差异很大。这项研究旨在报告一个有心脏问题史的五代家族中负责HCM的MYH7变体。方法：根据基于二维多普勒超声心动图或心血管磁共振的欧洲心脏病学会HCM标准建立诊断。使用下一代测序和Sanger方法进行遗传分析。结果：所介绍的家庭的病史始于先前父母健康的家庭的第一个孩子的HCM产前诊断。该家族的五代人都有长期的心源性猝死和心脏问题。ANM_000257.4：c.2342T>A（p。在MYH7基因中检测到Leu781Gln)变异。在先证者和大家庭中的所有受影响个体中，它都是杂合的。该变体存在于10名受影响的家庭成员中，并缺席了7名成员。该疾病的临床病程在几个家庭成员中很严重：三名家庭成员死于心脏猝死，一名患者需要心脏移植,三人做了间隔肌切除术,和三个需要植入式心律转复除颤器（ICD）植入。结论：在此，我们报告了一个MYH7变异体，负责HCM。家族性HCM主要以常染色体显性遗传模式遗传，这符合我们的研究。然而,该家族显示了广泛的HCM临床谱.在10个基因检测阳性的家庭成员中，有8个患有严重的疾病，2个具有轻度表型。这表明疾病的严重程度可能取决于其他因素，很可能是遗传的。
