Belmont John W
Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Genetics & Genomics Services, Inc., Houston, TX 77096, USA.
J Cardiovasc Dev Dis. 2022 Sep 21;9(10):315. doi: 10.3390/jcdd9100315.
Hypoplastic left heart syndrome (HLHS) is among the most severe cardiovascular malformations and understanding its causes is crucial to making progress in prevention and treatment. Genetic analysis is a broadly useful tool for dissecting complex causal mechanisms and it is playing a significant role in HLHS research. However, unlike classical Mendelian disorders where a relatively small number of genes are largely determinative of the occurrence and severity of the disease, the picture in HLHS is complex. De novo single-gene and copy number variant (CNV) disorders make an important contribution, but there is emerging evidence for causal contributions from lower penetrance and common variation. Integrating this emerging knowledge into clinical diagnostics and translating the findings into effective prevention and treatment remain challenges for the future.
左心发育不全综合征（HLHS）是最严重的心血管畸形之一，了解其病因对于在预防和治疗方面取得进展至关重要。基因分析是剖析复杂因果机制的广泛有用工具，并且在HLHS研究中发挥着重要作用。然而，与经典孟德尔疾病不同，在经典孟德尔疾病中相对少数的基因在很大程度上决定了疾病的发生和严重程度，HLHS的情况较为复杂。新发单基因和拷贝数变异（CNV）疾病起了重要作用，但越来越多的证据表明低外显率和常见变异也有因果贡献。将这些新出现的知识整合到临床诊断中，并将研究结果转化为有效的预防和治疗方法，仍然是未来面临的挑战。
