3rd Faculty of Medicine of Charles University, Centre of Research for Diabetes, Endocrinological Diseases and Clinical Nutrition, Ruská 87, 100 00 Prague 10, Czech Republic.
Diabetes Res Clin Pract. 2010 May;88(2):132-8. doi: 10.1016/j.diabres.2010.01.005. Epub 2010 Feb 4.
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.
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.
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.
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.
目的/假设：MODY（青年发病的成年型糖尿病）是一种常染色体显性遗传的糖尿病，具有显著的遗传异质性。新的导致 MODY 的突变仍在被发现。MODY 的基因确诊允许根据潜在的具体遗传功能障碍应用个体化治疗。新的 MODY 突变的检测有助于提供可能的 MODY 基因型的更完整的图景。
我们使用 HNF1A（肝细胞核因子 1-α）、HNF4A（肝细胞核因子 4-α）和 GCK（葡萄糖激酶）基因的直接测序，测试了 43 名具有 MODY 临床特征的成年捷克患者。
在三个捷克家族中，我们发现了三个我们认为导致 MODY 的新突变——两个 HNF1A 的错义突变[F268L（c.802T>C）和 P291S（c.871C>T）]和一个 GCK 的移码突变 V244fsdelG（c.729delG）。一些新的 HNF1A 突变携带者成功地从胰岛素转为格列齐特，而一些新的 GCK 突变携带者在从胰岛素或口服降糖药转为饮食时也有良好的临床反应。
我们在三个捷克家族中描述了三个新的 MODY 突变。MODY 突变的鉴定对突变携带者的治疗有重要影响。
