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

Frontiers in Endocrinology

Hassen Hadj Kacem¹  Maab Babiker Mansour¹  Mona Mahfood¹  Mohamed Abid²  Mouna Mnif-Feki²  Faten Hadj Kacem²  Wajdi Safi²  Mohamed Hadj Kacem³  Mariam Moalla³  Thouraya Kammoun⁴  Mongia Hachicha⁴ 

[1] Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates;Endocrinology Department, Hedi Chaker University Hospital, Sfax, Tunisia;Laboratory of Molecular and Cellular Screening Processes, Center of Biotechnology of Sfax, University of Sfax, Sfax, Tunisia;Pediatric Department, Hedi Chaker University Hospital, Sfax, Tunisia;

关键词: MODY;    genetic testing;    Sanger sequencing;    GCK;    HNF1A;    clinical exome sequencing;   

DOI  :  10.3389/fendo.2021.684018

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown