肥厚型心肌病(HCM)是一种常染色体显性心肌病,这是儿童或青少年心脏骤停的最常见原因之一。它的特征是心室肥厚(通常是左心室),小心室腔,在没有异常负荷(如高血压或主动脉瓣狭窄)的情况下,超声心动图发现心室舒张顺应性降低。HCM通常由编码肌节或肌节相关基因的基因突变引起。进行全外显子组测序(WES)以鉴定可能的致病基因。通过WES,我们在一名11岁的HCM女孩和一名6岁的HCM男孩中分别鉴定了LIM结构域结合蛋白3(LDB3)突变(R547Q和P323S).神经网络分析表明,LDB3(R547Q和P323S)突变降低了其蛋白稳定性,置信度分为-0.9211和-0.8967。STRUM服务器还证实突变降低了其蛋白质稳定性。因此,LDB3突变可能与遗传性HCM相关。据我们所知,这是首次报道LDB3杂合变体(R547Q和P323S)负责可遗传的HCM。
Hypertrophic cardiomyopathy (HCM) is an autosomal dominant cardiomyopathy, which is one of the most common reasons for cardiac arrest in children or adolescents. It is characterized by ventricular hypertrophy (usually left ventricle), small ventricular cavity, and reduced ventricular diastolic compliance found by echocardiography in the absence of abnormal load (such as hypertension or aortic stenosis). HCM is usually caused by mutations in genes encoding sarcomere or sarcomere-related genes. Whole exome sequencing (WES) is performed to identify probable causative genes. Through WES, we identified LIM domain-binding protein 3 (LDB3) mutations (R547Q and P323S) respectively in an 11-year-old HCM girl and a 6-year-old HCM boy. Neural network analyses showed that the LDB3 (R547Q and P323S) mutation decreased its protein stability, with confidence scores of -0.9211 and -0.8967. The STRUM server also confirmed that the mutation decreased its protein stability. Thus, LDB3 mutation may be associated with heritable HCM. To our knowledge, this is the first time to report LDB3 heterozygous variants (R547Q and P323S) responsible for heritable HCM.