Fardoun Manal, Dehaini Hassan, Kamar Amina, Bitar Fadi, Majdalani Marianne, El-Rassi Issam, Nemer Georges, Arabi Mariam
Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.
Department of Biology, American University of Beirut, Beirut, Lebanon.
Pediatr Cardiol. 2019 Jun;40(5):1084-1091. doi: 10.1007/s00246-019-02099-y. Epub 2019 Apr 6.
Congenital heart defects (CHDs) are the leading cause of death in infants under 1 year of age. Aberrations in the expression and function of cardiac transcription factors (TFs) are a major contributor to CHDs. Despite the numerous studies undertaken to functionally characterize these TFs, their exact role in different stages of cardiogenesis is still not fully elucidated. Here we focused on HEY2, a basic helix loop helix transcriptional repressor, and its potential role in human ventricular septal defects. Genetic analysis was performed based on sequencing of DNA and cDNA obtained from post-operational cardiac tissues and blood of 17 Lebanese patients with various CHDs. The screen covered the entire coding regions of the GATA4, NKX2.5, TBX5, TBX20 and HEY2 genes. Our results revealed two novel somatic mutations, namely p.Ala229Thr and p.161_190 del, affecting HEY2 in the diseased cardiac tissues of two patients with VSD. These results suggest a potential role of HEY2 in regulating ventricular septation in humans.
先天性心脏病（CHD）是1岁以下婴儿死亡的主要原因。心脏转录因子（TF）表达和功能的异常是CHD的主要促成因素。尽管已开展了大量研究来对这些TF进行功能表征，但其在心脏发生不同阶段的确切作用仍未完全阐明。在此，我们聚焦于HEY2，一种基本螺旋-环-螺旋转录抑制因子，及其在人类室间隔缺损中的潜在作用。基于对17名患有各种CHD的黎巴嫩患者术后心脏组织和血液中获取的DNA和cDNA进行测序，开展了基因分析。筛查涵盖了GATA4、NKX2.5、TBX5、TBX20和HEY2基因的整个编码区。我们的结果揭示了两个新的体细胞突变，即p.Ala229Thr和p.161_190 del，在两名室间隔缺损患者的患病心脏组织中影响HEY2。这些结果表明HEY2在调节人类心室分隔中具有潜在作用。
