Unraveling the genetic basis of MODY: insights from next-generation sequencing.

Abstract

Maturity-onset diabetes of the young (MODY) is an uncommon kind of monogenic diabetes. The major characteristics of MODY include not having insulin resistance and the absence of autoimmunity, early onset, and a family history suggesting autosomal-dominant inheritance. Nonetheless, genetic testing is necessary for diagnosis. The MODY-related genes CEL, ABCC8, PDX1, GCK, WFS1, HNF4A, HNF1A, and HNF1B were examined using Next Generation Sequencing (NGS) in this investigation. This study aimed to evaluate the genetic and clinical characteristics of patients referred with a preliminary diagnosis of MODY, retrospectively. A total of 30 patients (18 male and 12 female) participated, with ages ranging from 5 to 56. Eight distinct genetic variants were identified in 17 cases (57%). Pathogenic variants in the HNF1A gene have been identified. Likely pathogenic variants were found in CEL, ABCC8, GCK, and HNF4A. The genes APPL1, BLK, INS, KCNJ1, KLF11, NEUROD1, PAX4, RFX6, and ZFP57 were shown to be mutation-free. Four distinct pathogenic variants are found in this series. Unexpectedly high rates of pathogenic variants have been found in the HNF1A gene. In 27% of cases, there is a family history of vertically transmitted diabetes. The study highlights the importance of genetic testing for individuals with early-onset diabetes and a strong family history of the condition. Comprehensive genetic testing and increased public awareness are essential for MODY.