Utilizing the KCNJ11 Gene Mutations in Spotting Egyptian Patients With Permanent Neonatal Diabetes Who Can Benefit From Treatment Shift

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.ABCC8andKCNJ11were 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.

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Genes predisposing to neonatal diabetes mellitus and pathophysiology: Current findings

Yahaya

Anyebe

2020

NPM

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BACKGROUND: Precision medicine, described as a therapeutic procedure in which complex diseases are treated based on the causal gene and pathophysiology, is being considered for diabetes mellitus (DM). To this end, several monogenetic mutations in the beta cells have been linked with neonatal diabetes mellitus (NDM), however, the list of suspect genes is expansive, necessitating an update. This study, therefore, provides an update on NDM candidate genes and pathophysiology. RESULTS: Reputable online academic databases were searched for relevant information, which led to the identification of 43 genes whose mutations are linked to the condition. Of the linked genes, mutations in the KCNJ11, ABCC8, and INS genes as well as the genes on 6q24 chromosomal region are the most frequently implicated. Mutations in these genes can cause pancreatic agenesis and developmental errors, resulting in NDM in the first six to twelve months of birth. The clinical presentations of NDM include frequent urination, rapid breathing, and dehydration, among others. CONCLUSIONS: Monogenetic mutations in the beta cells may cause NDM with distinct pathophysiology from other DM. Treatment options that target NDM candidate genes and pathophysiology may lead to an improved treatment compared with the present generalized treatment for all forms of DM.

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Utilizing the KCNJ11 Gene Mutations in Spotting Egyptian Patients With Permanent Neonatal Diabetes Who Can Benefit From Treatment Shift

Abstract: Implementing the findings of this molecular analysis could have a major clinical and nationwide economic impact on world health, especially in developing countries.

Cited by 3 publications

References 15 publications

Early-onset diabetes in Africa: A mini-review of the current genetic profile

Early-onset diabetes in Africa: A mini-review of the current genetic profile

Early-onset diabetes in Africa: A mini-review of the current genetic profile

Genes predisposing to neonatal diabetes mellitus and pathophysiology: Current findings

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