1 Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, Institute for Infectious Disease and Molecular Medicine, University of Cape Town , Cape Town, South Africa .
2 School of Medical Sciences, University of Cape Coast , Cape Coast, Ghana .
OMICS. 2018 May;22(5):301-321. doi: 10.1089/omi.2018.0033.
Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated. We present an expert review on CHD with lessons learned on Africa. We found variable CHD phenotype prevalence in Africa across countries and populations. There are important gaps and paucity in genomic studies of CHD in African populations. Among the available genomic studies, the key findings in Africa were variants in GATA4 (P193H), MTHFR 677TT, and MTHFR 1298CC that were associated with atrial septal defect, ventricular septal defect (VSD), Tetralogy of Fallot (TOF), and patent ductus arteriosus phenotypes and 22q.11 deletion, which is associated with TOF. There were no data on epigenomic association of CHD in Africa, however, other studies have shown an altered expression of miR-421 and miR-1233-3p to be associated with TOF and hypermethylation of CpG islands in the promoter of SCO2 gene also been associated with TOF and VSD in children with non-syndromic CHD. These findings signal the urgent need to develop and implement genetic and genomic research on CHD to identify the hereditary and genome-environment interactions contributing to CHD. These projected studies would also offer comparisons on CHD pathophysiology between African and other populations worldwide. Genomic research on CHD in Africa should be developed in parallel with next generation technology policy research and responsible innovation frameworks that examine the social and political factors that shape the emergence and societal embedding of new technologies.
先天性心脏病（CHD）是出生时发现的结构畸形，患病率为 1%。CHD 的临床轨迹变化很大，因此需要强大的诊断和治疗方法。大多数 CHD 都需要进行主要的手术干预。在非洲，尽管生命科学基础设施有所进步，医学学者的教育水平也在提高，但有限的临床数据表明，CHD 的检测和矫正仍不如世界其他地区。但是，非洲 CHD 的发病机制和遗传学很少得到系统研究。我们提供了一篇关于 CHD 的专家综述，并借鉴了非洲的经验教训。我们发现，非洲各国和各人群的 CHD 表型患病率存在差异。非洲人群的 CHD 基因组研究存在重要的空白和不足。在现有的基因组研究中，非洲的主要发现是 GATA4（P193H）、MTHFR 677TT 和 MTHFR 1298CC 中的变异与房间隔缺损、室间隔缺损（VSD）、法洛四联症（TOF）和动脉导管未闭表型有关，以及 22q.11 缺失与 TOF 有关。非洲没有 CHD 表观基因组关联的数据，但其他研究表明，miR-421 和 miR-1233-3p 的表达改变与 TOF 有关，SCO2 基因启动子的 CpG 岛高甲基化也与非综合征性 CHD 患儿的 TOF 和 VSD 有关。这些发现表明，迫切需要开展和实施 CHD 的遗传和基因组研究，以确定导致 CHD 的遗传和基因组-环境相互作用。这些计划中的研究还将提供非洲和世界其他地区 CHD 病理生理学的比较。非洲的 CHD 基因组研究应与下一代技术政策研究和负责任的创新框架并行开展，这些研究将检查塑造新技术出现和社会嵌入的社会和政治因素。
