Tunisian Maturity-Onset Diabetes of the Young: A Short Review and a New Molecular and Clinical Investigation

Abstract

Introduction/AimsMaturity-Onset Diabetes of the Young (MODY) is a monogenic non-autoimmune diabetes with 14 different genetic forms. MODY-related mutations are rarely found in the Tunisian population. Here, we explored MODY related genes sequences among seventeen unrelated Tunisian probands qualifying the MODY clinical criteria.Materials and MethodsThe GCK and HNF1A genes were systematically analyzed by direct sequencing in all probands. Then, clinical exome sequencing of 4,813 genes was performed on three unrelated patients. Among them, 130 genes have been reported to be involved in the regulation of glucose metabolism, β-cell development, differentiation and function. All identified variants were analyzed according to their frequencies in the GnomAD database and validated by direct sequencing.ResultsWe identified the previously reported GCK mutation (rs1085307455) in one patient. The clinical features of the MODY2 proband were similar to previous reports. In this study, we revealed rare and novel alterations in GCK (rs780806456) and ABCC8 (rs201499958) genes with uncertain significance. We also found two likely benign alterations in HNF1A (rs1800574) and KLF11 (rs35927125) genes with minor allele frequencies similar to those depicted in public databases. No pathogenic variants have been identified through clinical exome analysis.ConclusionsThe most appropriate patients were selected, following a strict clinical screening approach, for genetic testing. However, the known MODY1-13 genes could not explain most of the Tunisian MODY cases, suggesting the involvement of unidentified genes in the majority of Tunisian affected families.

Exploring the Landscape of Latent Autoimmune Diabetes and Maturity Onset Diabetes of the Young in Africa: A Scoping Review

“…16 Sudan 17 and Kenya. 18 For MODY, four papers were identified from Tunisia [19][20][21][22] and one each from Morocco, 23 South Africa 24 and Sudan 25 that had evaluated the prevalence of MODY in those countries (Figure 2). The map representation of the studies based on the countries from which they were conducted has been shown in Figures 3a and 3b.…”

“…The current diabetes treatment was also recorded for some of the studies. [22][23][24] Clinical parameters can be used as prognostic markers for disease outcome. Thus, analysis of these parameters is important for understanding disease trajectory.…”

Identification of Two Rare Homozygote Missense Variants in the IRS1 Gene in a Patient With Early Gestational Diabetes: A Case Study

“…All variants with coverage greater than 20 were analyzed. A special focus was given to a list of 133 genes related to diabetes, glucose metabolism, and the insulin pathway [15]. In addition, the functional impacts of the selected coding variants were predicted using the following tools: Sorting Intolerant From Tolerant (SIFT) [16], Protein Variation Effect Analyzer (PROVEAN) [17], and Polymorphism Phenotyping v2 (PolyPhen-2) [18].…”