El Bouchikhi Ihssane, Bouguenouch Laila, Moufid Fatima Zohra, Belhassan Khadija, Samri Imane, Chaouti Amal, Houssaïni Mohammed Iraqui, Atmani Samir, Ouldim Karim
Laboratory of Medical Genetics and Oncogenetics, HASSAN II University Hospital, Fez, Morocco.
Molecular Biology Laboratory, Faculty of Medicine and Pharmacy, University of Sidi Mohammed Ben Abdellah, Fez, Morocco.
Eurasian J Med. 2020 Oct;52(3):283-287. doi: 10.5152/eurasianjmed.2020.19237.
Atrial septal defect (ASD) is one of the most common types of congenital heart disease (CHD). It is mainly caused by mutations of NK2 homeobox 5, GATA binding protein 4 (GATA4), and myosin heavy chain 6 in non-syndromic cases. This study aims to carry out, for the first time, the GATA4 mutation screening in a Moroccan population affected by ASD and compare the obtained mutation rate across populations.
A total of 33 patients were enrolled in this study. DNAs were extracted from peripheral blood samples, and we performed PCR-sequencing for GATA4 coding regions. Sequences were analyzed by sequence alignment and functional impact prediction tools. Mutation rate comparisons were performed by R software using the appropriate statistical tests.
We detected 7 variants, but no pathogenic mutation was revealed, except for Asn352= that was assessed by human splicing finder algorithms to have a potential impairing effect on the splicing mechanism. Until proven by in vitro functional studies, the current pathogenic mutation rate in our cohort seems to be 0%. Statistical comparison with previous studies from all over the world shows no significant difference. Seemingly, comparison of previous GATA4 mutation rates among tetralogy of Fallot (TOF) populations shows no significant difference.
The low rates of GATA4 mutations observed throughout ASD and TOF international populations may suggest a limited causality of GATA4 mutations in the main CHDs, which further confirms the co-involvement of additional genetic and/or environmental factors in the manifestation of these phenotypes.
房间隔缺损（ASD）是最常见的先天性心脏病（CHD）类型之一。在非综合征性病例中，它主要由NK2同源盒5、GATA结合蛋白4（GATA4）和肌球蛋白重链6的突变引起。本研究旨在首次对受ASD影响的摩洛哥人群进行GATA4突变筛查，并比较不同人群中获得的突变率。
本研究共纳入33例患者。从外周血样本中提取DNA，并对GATA4编码区进行PCR测序。通过序列比对和功能影响预测工具对序列进行分析。使用适当的统计检验，通过R软件进行突变率比较。
我们检测到7个变异，但未发现致病突变，不过通过人类剪接发现算法评估，Asn352 =对剪接机制可能有潜在损害作用。在体外功能研究证实之前，我们队列中目前的致病突变率似乎为0%。与世界各地先前研究的统计比较显示无显著差异。似乎，法洛四联症（TOF）人群中先前GATA4突变率的比较也无显著差异。
在整个ASD和TOF国际人群中观察到的GATA4突变率较低，这可能表明GATA4突变在主要CHD中的因果关系有限，这进一步证实了其他遗传和/或环境因素共同参与了这些表型的表现。
