Park Joonhong, Cho Yong Gon, Park Ha Wook, Cho Jung Sun
Department of Laboratory Medicine, Jeonbuk National University Medical School and Hospital, Jeonju, South Korea.
Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea.
Front Pediatr. 2021 Mar 30;9:609389. doi: 10.3389/fped.2021.609389. eCollection 2021.
Left ventricular non-compaction (LVNC) is a very rare primary cardiomyopathy with a genetic etiology, resulting from the failure of myocardial development during embryogenesis, and it carries a high risk of left ventricular dysfunction, thromboembolic phenomenon, and malignant arrhythmias. Here, we report the first case of familial LVNC in Korea, caused by a novel missense variant. We performed duo exome sequencing (ES) to examine the genome of the proband and his father. A 15-year-old boy was admitted for the evaluation of exertional dyspnea for 2 weeks. He was diagnosed with LVNC with a dilated cardiomyopathy phenotype [left ventricular end-diastolic dimension 60 mm, interventricular septal dimension 8.2 mm by transthoracic echocardiography (TTE)]. For the screening of familial cardiomyopathy, TTE and cardiac magnetic resonance imaging (cMRI) were performed, which revealed hypertrophic and isolated LVNC in the proband's father and sister, respectively. In particular, the cMRI revealed dense hypertrabeculation with focal aneurysmal changes in the apical septal wall in the proband's father. ES of the father-son duo identified a novel heterozygous c.668T>C variant of the gene (NM_001103.3:c.668T>C, p.Leu223Pro; no rsID) as the candidate cause of autosomal dominant LVNC. Sanger sequencing confirmed this novel variant in the proband, his father, and sister, but not in the proband's grandmother. Even within families harboring the same variant, a variable risk of adverse outcomes is common. Therefore, familial screening for patients with LVNC associated with variant should be performed for early detection of the LVNC phenotype associated with poor outcomes, such as dilated LVNC.
左心室心肌致密化不全（LVNC）是一种非常罕见的原发性心肌病，具有遗传病因，由胚胎发育过程中心肌发育失败引起，且具有左心室功能障碍、血栓栓塞现象和恶性心律失常的高风险。在此，我们报告韩国首例由新型错义变异导致的家族性LVNC病例。我们进行了双人外显子组测序（ES）以检测先证者及其父亲的基因组。一名15岁男孩因劳力性呼吸困难2周入院评估。他被诊断为具有扩张型心肌病表型的LVNC[经胸超声心动图（TTE）显示左心室舒张末期内径60mm，室间隔厚度8.2mm]。为筛查家族性心肌病，进行了TTE和心脏磁共振成像（cMRI），结果分别在先证者的父亲和妹妹中发现了肥厚型和孤立性LVNC。特别是，cMRI显示先证者父亲的心尖间隔壁有密集的肌小梁增粗并伴有局灶性动脉瘤样改变。父子二人的ES鉴定出该基因的一种新型杂合c.668T>C变异（NM_001103.3:c.668T>C，p.Leu223Pro；无rsID）作为常染色体显性LVNC的候选病因。Sanger测序在先证者、其父亲和妹妹中证实了这种新型变异，但在先证者的祖母中未发现。即使在携带相同变异的家族中，不良结局的风险也存在差异。因此，对于与该变异相关的LVNC患者应进行家族筛查，以便早期发现与不良结局相关的LVNC表型，如扩张型LVNC。
