Pathogenic variants in MYH7 cause a wide range of cardiac and skeletal muscle diseases with childhood or adult onset. These include dilated and/or hypertrophic cardiomyopathy, left ventricular non-compaction cardiomyopathy, congenital myopathies with multi-minicores and myofiber type disproportion, myosin storage myopathy, Laing distal myopathy and others (scapulo-peroneal or limb-girdle muscle forms). Here we report the results from molecular genetic analyses (NGS and Sanger sequencing) of 4 patients in two families with variable neuromuscular phenotypes with or without cardiac involvement. Interestingly, variants in MYH7 gene appeared to be the cause in all the cases. A novel nonsense variant c.5746C>T, p.(Gln1916Ter) was found in the patient in Family 1 who deceased at the age of 2 years 4 months with the clinical diagnosis of dilated cardiomyopathy, whose father died before the age of 40 years, due to cardiac failure with clinical diagnosis of suspected limb-girdle muscular dystrophy. A splice acceptor variant c.5560–2A>C in MYH7 was detected in the second proband and her sister, with late onset distal myopathy without cardiac involvement. These different phenotypes (muscular involvement with severe cardiomyopathy and pure late onset neuromuscular phenotype without heart involvement) may result from novel MYH7 variants, which most probably impact the LMM (light meromyosin) domain's function of the mature protein.

MYH7 中的致病变异会导致儿童或成人发病的多种心脏和骨骼肌疾病。这些包括扩张型和/或肥厚型心肌病、左心室非致密性心肌病、具有多微核和肌纤维类型不成比例的先天性肌病、肌球蛋白贮积肌病、Laing 远端肌病和其他（肩胛-腓骨或肢带肌形式）。在这里，我们报告了来自两个家族的 4 名患者的分子遗传分析（NGS 和 Sanger 测序）的结果，这些患者具有不同的神经肌肉表型，有或没有心脏受累。有趣的是，MYH7基因的变异似乎是所有病例的原因。一种新的无意义变体 c.5746C> T, p.(Gln1916Ter) 发现于家族 1 的患者中，患者 2 岁 4 个月，临床诊断为扩张型心肌病，其父亲在 40 岁之前因心力衰竭而死亡，临床诊断为疑似肢带型肌营养不良症。剪接受体变异c.5560-2A> ç在MYH7在第二先证者和她的妹妹检测，有没有心脏受累迟发性肌病远端。这些不同的表型（严重心肌病的肌肉受累和无心脏受累的纯迟发性神经肌肉表型）可能是由新的MYH7变体引起的，最有可能影响成熟蛋白的 LMM（轻肌球蛋白）结构域的功能。