Adadey Samuel Mawuli, Mensah Joy Afua, Acquah Kojo Sekyi, Abugri James, Osei-Yeboah Richard
West African Centre for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana; School of Medicine and Health Science, University for Development Studies, Tamale, Ghana.
College of Health Sciences, University of Ghana, Ghana.
Eur J Med Genet. 2023 Dec;66(12):104887. doi: 10.1016/j.ejmg.2023.104887. Epub 2023 Nov 21.
Early-onset diabetes is poorly diagnosed partly due to its heterogeneity and variable presentations. Although several genes have been associated with the disease, these genes are not well studied in Africa. We sought to identify the major neonatal, early childhood, juvenile, or early-onset diabetes genes in Africa; and evaluate the available molecular methods used for investigating these gene variants. A literature search was conducted on PubMed, Scopus, Africa-Wide Information, and Web of Science databases. The retrieved records were screened and analyzed to identify genetic variants associated with early-onset diabetes. Although 319 records were retrieved, 32 were considered for the current review. Most of these records (22/32) were from North Africa. The disease condition was genetically heterogenous with most cases possessing unique gene variants. We identified 22 genes associated with early-onset diabetes, 9 of which had variants (n = 19) classified as pathogenic or likely pathogenic (PLP). Among the PLP variants, IER3IP1: p.(Leu78Pro) was the variant with the highest number of cases. There was limited data from West Africa, hence the contribution of genetic variability to early-onset diabetes in Africa could not be comprehensively evaluated. It is worth mentioning that most studies were focused on natural products as antidiabetics and only a few studies reported on the genetics of the disease. ABCC8 and KCNJ11 were implicated as major contributors to early-onset diabetes gene networks. Gene ontology analysis of the network associated ion channels, impaired glucose tolerance, and decreased insulin secretions to the disease. Our review highlights 9 genes from which PLP variants have been identified and can be considered for the development of an African diagnostic panel. There is a gap in early-onset diabetes genetic research from sub-Saharan Africa which is much needed to develop a comprehensive, efficient, and cost-effective genetic panel that will be useful in clinical practice on the continent and among the African diasporas.
早发性糖尿病的诊断存在困难，部分原因是其具有异质性和多样的临床表现。尽管有几个基因与该疾病相关，但这些基因在非洲尚未得到充分研究。我们试图确定非洲主要的新生儿、幼儿、青少年或早发性糖尿病基因；并评估用于研究这些基因变异的现有分子方法。我们在PubMed、Scopus、非洲全信息数据库和科学网数据库上进行了文献检索。对检索到的记录进行筛选和分析，以确定与早发性糖尿病相关的基因变异。尽管检索到319条记录，但本综述仅考虑了32条。这些记录中的大多数（22/32）来自北非。该疾病在基因上具有异质性，大多数病例拥有独特的基因变异。我们确定了22个与早发性糖尿病相关的基因，其中9个基因的变异（n = 19）被分类为致病性或可能致病性（PLP）。在PLP变异中，IER3IP1:p.(Leu78Pro)是病例数最多的变异。来自西非的数据有限，因此无法全面评估基因变异性对非洲早发性糖尿病的影响。值得一提的是，大多数研究集中在天然产物作为抗糖尿病药物，只有少数研究报道了该疾病的遗传学。ABCC8和KCNJ11被认为是早发性糖尿病基因网络的主要贡献者。对该网络的基因本体分析表明离子通道、糖耐量受损和胰岛素分泌减少与该疾病有关。我们的综述强调了9个已鉴定出PLP变异的基因，可考虑用于开发非洲诊断面板。撒哈拉以南非洲的早发性糖尿病基因研究存在差距，这对于开发一个全面、高效且具有成本效益的基因面板至关重要，该面板将在非洲大陆及非洲侨民的临床实践中发挥作用。
