Akademik Veri Yönetim Sistemi
European Human Genetics Conference, Milan, İtalya, 24 - 27 Mayıs 2025, ss.15-16, (Özet Bildiri)
Background:
Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes. MODY is a genetically heterogeneous disease. So far, 14 different subtypes associated with 14 different genes have been described. Next-generation sequencing technologies have been increasingly used in recent years for MODY's molecular diagnosis. In the first step, multigene targeted panels for known genes are applied, but the genetic etiology remains unexplained in approximately 20-30% of patients (MODY-X). In this study, we aimed to identify additional genes and variants in the MODY-X patients.
Materials and Methods:
In this study, whole exome sequencing of peripheral blood was performed in 5 patients and their affected first-degree relatives (5 families, n=10) who were admitted to Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Medical Genetics between 2020 and 2023 with a prediagnosis of MODY and whose genetic diagnosis could not be established by multigene targeted panels for the etiology of MODY.
Results:
Two novel variants in GIGYF1 gene in 2 different families and 1 novel variant in SLC30A8 gene in 3 individuals from 2 different families were detected. In addition, variants considered to be significant in GCKR, MAPK8IP1, ITPR3, ONECUT1 genes, which were previously reported as candidate genes of monogenic diabetes and RFX7, RAP1GAP, EXOC7 genes, which were not previously shown in diabetic patients, were detected.
Conclusion:
Whole exome sequencing contributes to deepen genetic research, identify new genes and variants and better understand the molecular pathogenesis of the disease, especially in the MODY-X patient group where targeted panels are insufficient to make a diagnosis. In addition to genes previously associated with diabetes, this study identified new candidate genes that may be associated with MODY. This is the first whole exome sequencing study of this scale in the MODY-X group in the Turkish population.