Andreeva Sofiya, Chumakova Olga, Karelkina Elena, Lebedeva Viktoriya, Lubimtseva Tamara, Semenov Andrey, Nikitin Alexey, Speshilov Gleb, Kozyreva Alexandra, Sokolnikova Polina, Zhuk Sergey, Fomicheva Yuliya, Moiseeva Olga, Kostareva Anna
Institute of Molecular Biology and Genetics and World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russia.
Central State Medical Academy of Department of Presidential Affairs, City Clinical Hospital #17, Moscow, Russia.
Front Genet. 2022 Feb 22;13:743472. doi: 10.3389/fgene.2022.743472. eCollection 2022.
Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary diseases, and it is associated with fatal complications. The clinical heterogeneity of HCM requires risk prediction models to identify patients at a high risk of adverse events. Most HCM cases are caused by mutations in genes encoding sarcomere proteins. However, HCM is associated with rare genetic variants with limited data about its clinical course and prognosis, and existing risk prediction models are not validated for such patients' cohorts. is one of the rare genes recently described as a cause of HCM with autosomal-recessive inheritance. Herein, we present two cases of HCM associated with -compound heterozygous variants in young male sportsmen. They demonstrated progressively marked hypertrophy, advanced diastolic dysfunction, a significant degree of fibrosis detected by magnetic resonance imaging, and clear indications for implantable cardioverter-defibrillator. One of the cases includes the first description of -HCM with extreme hypertrophy. The presented cases are discussed in light of molecular consequences that might underlie cardiac and muscle phenotype in patients with mutations of , the master regulator of striated muscle mass.
肥厚型心肌病（HCM）是最常见的遗传性疾病之一，且与致命并发症相关。HCM的临床异质性需要风险预测模型来识别发生不良事件风险高的患者。大多数HCM病例由编码肌节蛋白的基因突变引起。然而，HCM与罕见的基因变异相关，关于其临床病程和预后的数据有限，并且现有的风险预测模型尚未在这类患者队列中得到验证。 是最近被描述为常染色体隐性遗传的HCM病因的罕见基因之一。在此，我们报告两例年轻男性运动员中与 -复合杂合变异相关的HCM病例。他们表现出进行性显著肥厚、晚期舒张功能障碍、磁共振成像检测到显著程度的纤维化以及植入式心脏复律除颤器的明确指征。其中一例病例首次描述了具有极度肥厚的 -HCM。结合 （横纹肌质量的主要调节因子）突变患者心脏和肌肉表型潜在的分子后果，对所报告的病例进行了讨论。
