The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study

• Published in: International journal of molecular sciences Vol. 24; no. 1; p. 130
• Main Authors: Elashi, Asma A., Toor, Salman M., Diboun, Ilhame, Al-Sarraj, Yasser, Taheri, Shahrad, Suhre, Karsten, Abou-Samra, Abdul Badi, Albagha, Omar M. E.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 21.12.2022
• Subjects: Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Hepatocyte Nuclear Factor 1-alpha - genetics; Humans; Mutation; Qatar - epidemiology; Qatar; MODY; HNF1A; maturity-onset diabetes of the young; diabetes; HNF4A; GCK
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms24010130

Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes mellitus. In this study, we estimated the prevalence and genetic spectrum of MODY in the Middle Eastern population of Qatar using whole-genome sequencing (WGS) of 14,364 subjects from the population-based Qatar biobank (QBB) cohort. We focused our investigations on 14 previously identified genes ascribed to the cause of MODY and two potentially novel MODY-causing genes, RFX6 and NKX6-1. Genetic variations within the 16 MODY-related genes were assessed for their pathogenicity to identify disease-causing mutations. Analysis of QBB phenotype data revealed 72 subjects (0.5%) with type 1 diabetes, 2915 subjects (20.3%) with type 2 diabetes and 11,377 (79.2%) without diabetes. We identified 22 mutations in 67 subjects that were previously reported in the Human Genetic Mutation Database (HGMD) as disease-causing (DM) or likely disease causing (DM?) for MODY. We also identified 28 potentially novel MODY-causing mutations, predicted to be among the top 1% most deleterious mutations in the human genome, which showed complete (100%) disease penetrance in 34 subjects. Overall, we estimated that MODY accounts for around 2.2–3.4% of diabetes patients in Qatar. This is the first population-based study to determine the genetic spectrum and estimate the prevalence of MODY in the Middle East. Further research to characterize the newly identified mutations is warranted.