Li Tiange, Jin Yuxi, Liu Rui, Hua Yimin, Zhou Kaiyu, Luo Shuhua, Li Yifei, Zhang Donghui
Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
Front Cardiovasc Med. 2023 Jun 15;10:1212417. doi: 10.3389/fcvm.2023.1212417. eCollection 2023.
Malignant hypertrophic cardiomyopathy (HCM) phenotypes have potential risks of severe heart failure, fatal arrhythmia, and sudden cardiac death. Therefore, it is critical to predict the clinical outcomes of these patients. It was reported recently that the alpha kinase 3 () gene was involved in the occurrence of HCM. Herein we reported a girl with HCM, while whole-exome sequencing found novel compound heterozygous variants in gene, which identified a potential association.
We reported a 14-year-girl who suffered from clinical manifestations of cardiac failure, with sudden cardiac arrest before admission. The heartbeat recovered after cardiopulmonary resuscitation, though she remained unconscious without spontaneous breath. The patient stayed comatose when she was admitted. Physical examination indicated enlargement of the heart boundary. Laboratory results revealed a significant increment of myocardial markers, while imaging demonstrated hypertrophy of the left heart and interventricular septum. Whole-exome sequencing (WES) identified a compound heterozygous variant in gene consisting of c.3907_3922del and c.2200A>T, which was inherited from her parents. Both variants (p.G1303Lfs28 and p.R734) were disease-causing evaluated by MutationTaster (probability 1.000). The crystal structure of the complete amino acid sequence is predicted and evaluated by AlphaFold and SWISS-MODEL software (July, 2022), which revealed three domains. Moreover, both variants resulted in a wide protein-truncating variant and damaged protein function. Thus, a novel compound heterozygous variant in associated with HCM was diagnosed.
We described a young patient with -associated HCM who experienced sudden cardiac arrest. Through WES, we identified a compound heterozygous variant in the gene, c.3907_3922del and c.2200A>T, which were inherited from the patient's parents and resulted in a truncated protein, indirectly causing the symptoms of HCM. In addition, WES provided clues in evaluating potential risks of gene variants on fatal clinical outcomes, and the nonsense and frameshift variants of were related to adverse clinical outcomes in HCM patients, which required implantable cardioverter defibrillator (ICD) timely.
恶性肥厚型心肌病（HCM）表型具有严重心力衰竭、致命性心律失常和心源性猝死的潜在风险。因此，预测这些患者的临床结局至关重要。最近有报道称，α激酶3（）基因与HCM的发生有关。在此，我们报告了一名患有HCM的女孩，全外显子测序在基因中发现了新的复合杂合变异，确定了一种潜在关联。
我们报告了一名14岁女孩，有心力衰竭的临床表现，入院前发生心搏骤停。心肺复苏后心跳恢复，但她仍昏迷且无自主呼吸。入院时患者仍处于昏迷状态。体格检查显示心界扩大。实验室检查结果显示心肌标志物显著升高，影像学检查显示左心室和室间隔肥厚。全外显子测序（WES）在基因中鉴定出一个复合杂合变异，由c.3907_3922del和c.2200A>T组成，该变异遗传自她的父母。通过MutationTaster评估，这两个变异（p.G1303Lfs28和p.R734）均为致病变异（概率为1.000）。使用AlphaFold和SWISS-MODEL软件（2022年7月）对完整氨基酸序列的晶体结构进行预测和评估，结果显示有三个结构域。此外，这两个变异均导致广泛的蛋白质截短变异并损害蛋白质功能。因此，诊断出一种与HCM相关的新的复合杂合变异。
我们描述了一名患有与相关的HCM且经历心搏骤停的年轻患者。通过WES，我们在基因中鉴定出一个复合杂合变异，即c.3907_3922del和c.2200A>T，该变异遗传自患者父母并导致蛋白质截短，间接引起HCM症状。此外，WES为评估基因变异对致命临床结局的潜在风险提供了线索，基因的无义变异和移码变异与HCM患者的不良临床结局相关，这需要及时植入植入式心律转复除颤器（ICD）。
