Vecoli Cecilia, Pulignani Silvia, Foffa Ilenia, Andreassi Maria Grazia
CNR, Institute of Clinical Physiology, Pisa, Italy.
CNR, Institute of Clinical Physiology, Massa, Italy;
Curr Genomics. 2014 Oct;15(5):390-9. doi: 10.2174/1389202915666140716175634.
Congenital heart diseases (CHDs) are recognized as the most common type of birth malformations. Although recent advances in pre- and neonatal diagnosis as well as in surgical procedures have reduced the morbidity and mortality for many CHD, the etiology for CHD remains undefined. In non-syndromic and isolated (without a familial history or a Mendelian inheritance) forms of CHDs, a multifactorial pathogenesis with interplay between inherited and non-inherited causes is recognized. In this paper, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal cardiac development in non-syndromic and isolated CHD, including mutations in cardiac transcription factors, the role of somatic mutations and epigenetic alterations as well as the influence of gene-environment interactions. In the near future, the advent of high-throughput genomic technologies with the integration of system biology will expand our understanding of isolated, non-syndromic CHDs for their prevention, early diagnosis and therapy.
先天性心脏病（CHD）被认为是最常见的出生缺陷类型。尽管近年来产前和新生儿诊断以及外科手术方面的进展降低了许多先天性心脏病的发病率和死亡率，但先天性心脏病的病因仍不明确。在非综合征性和孤立性（无家族病史或孟德尔遗传）的先天性心脏病中，人们认识到存在一种多因素发病机制，涉及遗传和非遗传因素之间的相互作用。在本文中，我们讨论了目前关于潜在分子机制的知识，这些机制介导了非综合征性和孤立性先天性心脏病中异常的心脏发育，包括心脏转录因子的突变、体细胞突变和表观遗传改变的作用以及基因-环境相互作用的影响。在不久的将来，高通量基因组技术与系统生物学的整合将扩展我们对孤立性、非综合征性先天性心脏病的认识，从而实现其预防、早期诊断和治疗。
