The genetic etiology and heritability of left ventricular noncompaction (LVNC) in adults is unclear. This study sought to assess the value of genetic testing in adults with LVNC. Adults diagnosed with LVNC while undergoing screening in the context of a family history of cardiomyopathy were excluded. Clinical data for 35 unrelated patients diagnosed with LVNC at ≥18 years of age were retrospectively analyzed. Left ventricular (LV) dysfunction, electrocardiogram (ECG) abnormalities, cardiac malformations or syndromic features were identified in 25 patients; 10 patients had isolated LVNC in the absence of cardiac dysfunction or syndromic features. Exome sequencing was performed, and analysis using commercial panels targeted 193 nuclear and mitochondrial genes. Nucleotide variants in coding regions or in intron-exon boundaries with predicted impacts on splicing were assessed. Fifty-four rare variants were identified in 35 nuclear genes. Across all 35 LVNC patients, the clinically meaningful genetic diagnostic yield was 9% (3/35), with heterozygous likely pathogenic or pathogenic variants identified in the NKX2-5 and TBX5 genes encoding cardiac transcription factors. No pathogenic variants were identified in patients with isolated LVNC in the absence of cardiac dysfunction or syndromic features. In conclusion, the diagnostic yield of genetic testing in adult index patients with LVNC is low. Genetic testing is most beneficial in LVNC associated with other cardiac and syndromic features, in which it can facilitate correct diagnoses, and least useful in adults with only isolated LVNC without a family history. Cardiac transcription factors are important in the development of LVNC and should be included in genetic testing panels.

成人左心室致密化不全（LVNC）的遗传病因和遗传性尚不清楚。本研究旨在评估基因检测对成人 LVNC 的价值。在有心肌病家族史的情况下接受筛查时被诊断为 LVNC 的成年人被排除在外。回顾性分析35例年龄≥18岁诊断为LVNC的无关患者的临床资料。 25 名患者出现左心室 (LV) 功能障碍、心电图 (ECG) 异常、心脏畸形或综合征特征； 10 名患者在没有心功能障碍或综合征特征的情况下出现孤立性 LVNC。进行了外显子组测序，并使用商业面板对 193 个核和线粒体基因进行了分析。评估了编码区或内含子-外显子边界中的核苷酸变异以及对剪接的预测影响。在 35 个核基因中鉴定出 54 个罕见变异。在所有 35 名 LVNC 患者中，具有临床意义的遗传诊断率为 9% (3/35)，在编码心脏转录因子的NKX2-5和TBX5基因中鉴定出杂合的可能致病或致病变异。在没有心功能障碍或综合征特征的孤立性 LVNC 患者中，未发现致病变异。总之，基因检测对成年 LVNC 患者的诊断率较低。基因检测对于与其他心脏和综合征特征相关的 LVNC 最为有益，可以促进正确诊断，而对于仅有孤立性 LVNC 而没有家族史的成人则效果最差。心脏转录因子在 LVNC 的发展中很重要，应包含在基因检测组中。