Three novel mutations in MODY and its phenotype in three different Czech families

Abstract Aims/hypothesis MODY (Maturity Onset Diabetes of the Young) is an autosomal dominant inherited type of diabetes with significant genetic heterogeneity. New mutations causing MODY are still being found. A genetically confirmed diagnosis of MODY allows application of individualized treatment based on the underlying concrete genetic dysfunction. Detection of novel MODY mutations helps provide a more complete picture of the possible MODY genotypes. Materials and methods We tested 43 adult Czech patients with clinical characteristics of MODY, using direct sequencing of HNF1A (hepatocyte nuclear factor 1-alpha), HNF4A (hepatocyte nuclear factor 4-alpha) and GCK (glucokinase) genes. Results In three Czech families we identified three novel mutations we believe causing MODY—two missense mutations in HNF1A [F268L (c.802T > C) and P291S (c.871C > T)] and one frame shift mutation in GCK V244fsdelG ( c.729delG ). Some of the novel HNF1A mutation carriers were successfully transferred from insulin to gliclazide, while some of the novel GCK mutation carriers had a good clinical response when switched from insulin or oral antidiabetic drugs to diet. Conclusion We describe three novel MODY mutations in three Czech families. The identification of MODY mutations had a meaningful impact on therapy on the mutation carriers.