BACKGROUND Left ventricular noncompaction cardiomyopathy (LVNC) is a primary cardiomyopathy with an unclear aetiology. The clinical symptoms range from asymptomatic to heart failure, arrhythmias and sudden cardiac death. This study aimed to characterize the genetic features and clinical outcomes of LVNC who underwent heart transplantation (HTx) to reveal the potential genetic pathogenesis. METHODS AND RESULTS We recruited 16 cases who underwent HTx in our hospital. Exome-sequencing was performed to reveal genetic background. Clinical information and histopathology features of patients were investigated. Gene expression profiling of tissue fibrosis were evaluated by quantitative PCR. The median age of patients was 21 years. Of the 16 patients, 14 harboured multiple gene variants involved in LVNC. Ten of the patients harboured biallelic variants and/or truncating variants. Young patients (<18) with biallelic variants and/or truncating variants and lower LVEF (<45%) at initial symptom deteriorated quickly. Except for noncompaction myocardium, myocardial fibrosis was a remarkable pathological feature, and gene profiles related to immune inflammation and extracellular matrix remodelling were upregulated. CONCLUSIONS This study showed that multiple pathologic variants were underlie genetic mechanism of LVNC who in high risks, suggesting that genetic screening should be applied to the diagnosis of LVNC. LVNC patient with multiple variants should be considered carefully follow-up. Genetics involved in the phenotype and cardiac fibrosis, and is the major causing for LVNC.

中文翻译：

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青少年左心室非紧致型心肌病的多种遗传变异。

背景技术左心室非紧致型心肌病（LVNC）是一种病因不明的原发性心肌病。临床症状范围从无症状到心力衰竭，心律不齐和心源性猝死。这项研究旨在表征接受心脏移植（HTx）的LVNC的遗传特征和临床结局，以揭示潜在的遗传病机。方法和结果我们招募了在我院接受HTx治疗的16例患者。进行外显子组测序以揭示遗传背景。研究了患者的临床信息和组织病理学特征。通过定量PCR评估组织纤维化的基因表达谱。患者的中位年龄为21岁。在16例患者中，有14例包含涉及LVNC的多种基因变异。其中十名患者携带双等位基因变异和/或截短变异。年轻患者（<18岁）有双等位基因变异和/或截短变异且初发症状时LVEF较低（<45％）迅速恶化。除非致密性心肌外，心肌纤维化是一个显着的病理特征，与免疫炎症和细胞外基质重塑有关的基因谱也被上调。结论这项研究表明，多种病理变异是高危人群LVNC遗传机制的基础，这表明基因筛查应用于LVNC的诊断。LVNC患者有多种变异应仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。18）具有双等位基因变体和/或截短变体，初始症状下的LVEF较低（<45％）迅速恶化。除非致密性心肌外，心肌纤维化是一个显着的病理特征，与免疫炎症和细胞外基质重塑有关的基因谱也被上调。结论这项研究表明，多种病理变异是高危人群LVNC遗传机制的基础，这表明基因筛查应用于LVNC的诊断。LVNC患者有多种变异，应考虑仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。18）具有双等位基因变体和/或截短变体，初始症状下的LVEF较低（<45％）迅速恶化。除非致密性心肌外，心肌纤维化是一个显着的病理特征，与免疫炎症和细胞外基质重塑有关的基因谱也被上调。结论这项研究表明，多种病理变异是高危人群LVNC遗传机制的基础，这表明基因筛查应用于LVNC的诊断。LVNC患者有多种变异，应考虑仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。心肌纤维化是一个显着的病理特征，与免疫炎症和细胞外基质重塑有关的基因谱被上调。结论这项研究表明，多种病理变异是高危人群LVNC遗传机制的基础，这表明基因筛查应用于LVNC的诊断。LVNC患者有多种变异，应考虑仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。心肌纤维化是一个显着的病理特征，与免疫炎症和细胞外基质重塑有关的基因谱被上调。结论这项研究表明，多种病理变异是高危人群LVNC遗传机制的基础，这表明基因筛查应用于LVNC的诊断。LVNC患者有多种变异，应考虑仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。提示应将基因筛查用于LVNC的诊断。LVNC患者有多种变异，应考虑仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。提示应将基因筛查用于LVNC的诊断。LVNC患者有多种变异，应考虑仔细随访。遗传涉及表型和心脏纤维化，是导致LVNC的主要原因。