The Mutation Spectrum of Maturity Onset Diabetes of the Young (MODY)-Associated Genes among Western Siberia Patients.
Dinara E IvanoshchukElena V ShakhtshneiderOksana D RymarAlla K OvsyannikovaSvetlana V MikhailovaVeniamin S FishmanEmil S ValeevPavel S OrlovMikhail I VoevodaPublished in: Journal of personalized medicine (2021)
Maturity onset diabetes of the young (MODY) is a congenital form of diabetes characterized by onset at a young age and a primary defect in pancreatic-β-cell function. Currently, 14 subtypes of MODY are known, and each is associated with mutations in a specific gene: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1. The most common subtypes of MODY are associated with mutations in the genes GCK, HNF1A, HNF4A, and HNF1B. Among them, up to 70% of cases are caused by mutations in GCK and HNF1A. Here, an analysis of 14 MODY genes was performed in 178 patients with a MODY phenotype in Western Siberia. Multiplex ligation-dependent probe amplification analysis of DNA samples from 50 randomly selected patients without detectable mutations did not reveal large rearrangements in the MODY genes. In 38 patients (37% males) among the 178 subjects, mutations were identified in HNF4A, GCK, HNF1A, and ABCC8. We identified novel potentially causative mutations p.Lys142*, Leu146Val, Ala173Glnfs*30, Val181Asp, Gly261Ala, IVS7 c.864 -1G>T, Cys371*, and Glu443Lys in GCK and Ser6Arg, IVS 2 c.526 +1 G>T, IVS3 c.713 +2 T>A, and Arg238Lys in HNF1A.
Keyphrases
- end stage renal disease
- nuclear factor
- genome wide
- type diabetes
- ejection fraction
- newly diagnosed
- chronic kidney disease
- cardiovascular disease
- gene expression
- single cell
- dna methylation
- patient reported outcomes
- middle aged
- genome wide analysis
- high throughput
- patient reported
- bioinformatics analysis
- living cells
- circulating tumor
- weight loss