Abstrakt
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.727-728delG)].
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.