Lopez A P, Foscaldi S A, Pérez M S, Krochik G, Rodríguez M, Traversa M, Puchulu F M, Hirschler V, Bergada I, Frechtel G D
Department of Genetics and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Exp Clin Endocrinol Diabetes. 2009 Sep;117(8):391-4. doi: 10.1055/s-0029-1214427. Epub 2009 Apr 8.
Mutations in the glucokinase gene (GCK) produce a subtype of Maturity onset diabetes in the young (MODY), named MODY 2. To date over than 190 different mutations have been identified, distributed over the coding regions and the exon-intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the GCK gene, in a MODY clinically characterized Argentinean population.
Seventy unrelated individuals were selected based on MODY clinical features. The study methodology consisted in PCR amplification of the coding regions of the GCK gene, SSCP electrophoresis analysis of the amplified fragments and direct sequencing of the fragments with abnormal electrophoresis pattern.
We identified a total of six patients with mutations in the GCK gene. This included two novel mutations: g.1831C>A, g.3792T>A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of MODY 2 among the patients in study reaching to 8.6%.
The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of MODY 2 in the population under study. These findings contribute to confirm the allelic heterogeneity of GCK gene mutations and may provide an insight into the structure-function relationship of the GCK.
葡萄糖激酶基因（GCK）突变会导致青少年成年起病型糖尿病（MODY）的一种亚型，称为MODY 2。迄今为止，已鉴定出190多种不同的突变，分布在该基因的编码区和外显子-内含子边界。本研究的目的是在具有MODY临床特征的阿根廷人群中，研究GCK基因突变的性质和频率。
根据MODY临床特征选择了70名无亲缘关系的个体。研究方法包括GCK基因编码区的PCR扩增、扩增片段的单链构象多态性（SSCP）电泳分析以及电泳图谱异常片段的直接测序。
我们共鉴定出6名GCK基因突变患者。其中包括两个新突变：g.1831C>A、g.3792T>A，一个已由我们的研究小组报道过的g.168fsdelC（两名无亲缘关系的患者中出现相同突变）以及两个已报道过的突变：p.Gln138Pro和p.Gly261Glu。根据这些数据，我们可以确定研究患者中MODY 2的患病率达到8.6%。
本研究的主要贡献在于报告了迄今为止未描述的两个新突变，并探讨了研究人群中MODY 2患病率的确定方法。这些发现有助于证实GCK基因突变的等位基因异质性，并可能为GCK的结构-功能关系提供见解。
