The Application of Next Generation Sequencing Maturity Onset Diabetes of the Young Gene Panel in Turkish Patients from Trakya Region

Objective The aim of this study was to investigate the molecular basis of maturity-onset diabetes of the young by targeted-gene sequencing of 20 genes related to monogenic diabetes and estimate the frequency and describe the clinical characteristics of monogenic diabetes and MODY in Trakya Region of Turkey. Methods In 61 cases, a panel of 20 monogenic diabetes related genes were screened. Illumina NextSeq550 system was used for sequencing of the genes. Pathogenicity of the variants were assessed by bioinformatics prediction software programs and segregation analyses. Results In 29 (47,5%) cases, 31 pathogenic/likely pathogenic variants in the GCK, ABCC8, KCNJ11, HNF1A, HNF4A genes and in 11 (18%) cases, 14 variants of uncertain significance in the GCK, RFX6, CEL, PDX1, KCNJ11, HNF1A, G6PC2, GLIS3 and KLF11 genes were identified. 6 different pathogenic/likely pathogenic variants and 6 different variants of uncertain significance were detected as novel. Conclusions This is the first study including molecular studies of twenty monogenic diabetes genes in Turkish cases in Trakya Region. The results of this study showed that pathogenic variants in the GCK gene are the leading cause of MODY in our population. A high frequency of novel variants (32.4%-12/37) in the current study, suggests that multiple gene analysis provides accurate genetic diagnosis in MODY.