Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Athens University School of Medicine, 'Agia Sophia' Children's Hospital, Athens, Greece.
Pediatr Diabetes. 2013 Nov;14(7):526-34. doi: 10.1111/pedi.12032. Epub 2013 Mar 21.
Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1-2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients.
Three hundred ninety-five patients were referred to our center because of suspected MODY during a period of 15 yr. The use of Denaturing Gradient Gel Electrophoresis of polymerase chain reaction amplified DNA revealed 72 patients carrying Glucokinase gene mutations (MODY2) and 8 patients carrying HNF1A gene mutations (MODY3). After using strict criteria, 54 patients were selected to be further evaluated by direct sequencing or by multiplex ligation probe amplification (MLPA) for the presence of HNF1A gene mutations.
In 16 unrelated patients and 13 of their relatives, 15 mutations were identified in the HNF1A gene. Eight of these mutations were previously reported, whereas seven were novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location.
In our cohort of patients fulfilling strict clinical criteria for MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene are responsible for a significant proportion of monogenic diabetes in the Greek population. No clear phenotype-genotype correlations were identified.
青年发病的成年型糖尿病（MODY）是最常见的单基因糖尿病类型，占糖尿病患者的 1-2%。在欧洲国家，HNF1A-MODY（MODY3）的相对发病率较高；然而，希腊人群的数据尚不清楚。本研究的目的是确定 MODY3 在希腊的相对频率、观察到的突变类型及其与患者表型的关系。
在 15 年的时间里，由于疑似 MODY，395 名患者被转诊到我们中心。聚合酶链反应扩增 DNA 的变性梯度凝胶电泳的使用显示 72 名患者携带葡萄糖激酶基因突变（MODY2），8 名患者携带 HNF1A 基因突变（MODY3）。在用严格的标准筛选后，选择 54 名患者进行进一步评估，通过直接测序或多重连接探针扩增（MLPA）检测 HNF1A 基因突变。
在 16 名无关患者及其 13 名亲属中，在 HNF1A 基因中发现了 15 种突变。其中 8 种突变是先前报道的，而 7 种是新的。临床特征，如糖尿病的发病年龄或高血糖的严重程度，与突变类型或位置无关。
在我们符合 MODY 严格临床标准的患者队列中，12%携带 HNF1A 基因突变，表明该基因的缺陷是希腊人群中单基因糖尿病的重要原因。未发现明确的表型-基因型相关性。
