两个MODY2中国家系葡萄糖激酶基因杂合突变的研究  

Study of two heterozygous mutations of glucokinase(GCK) gene in two MODY2 Chinese pedigrees

作　　者：刁呈明[1] 萨仁图雅[2] 肖新华[1] 孙晓方[1] 茅李莉[1] 张茜[1] 李文慧[1] 于淼[1] 袁涛[1] 黎明[1] 向红丁[1] 王姮[1] 

机构地区：[1]中国医学科学院北京协和医学院、北京协和医院内分泌科,卫生部内分泌重点实验室,100730 [2]北京市朝阳糖尿病医院

出　　处：《中国糖尿病杂志》2010年第6期405-408,共4页Chinese Journal of Diabetes

基　　金：北京市自然科学基金资助项目(7092085)

摘　　要：目的寻找两个典型的MOIDY2家系的责任基因。方法抽提两个MODY2家系成员基因组DNA,PCR扩增、直接测序候选基因葡萄糖激酶(GCK)基因5′端、3′端非翻译区及1～10号外显子,确认突变。结果家系1中4人携带GCK基因杂合突变c.661G>A(E221K),先证者为MOIDY2,另2名突变携带者表现为糖调节受损(IGR),1名突变携带者血糖正常。家系2中2人携带GCK基因杂合突变c.771G>A(W257ter),先证者为MOIDY2,另1名突变携带者表现为IGR。在这些患者中,饮食控制和增强运动能收到良好效果。结论 GCK基因突变c.661G>A(E221K)和c.771G>A(W257ter)可能是两个MOIDY2家系的主要致病基因,其中c.771G>A(W257ter)是一个新发现的突变位点。Objective To identify the related genes for two MODY2 chinese pedigrees. Methods The genomic DNA of all members in the pedigrees was extracted, followed by PCR amplification on 5＂, 3＇ untranslated regions and exons 1 to 10 of GCK gene. Sequencing in both directions were performed to identify mutations on GCK gene. Results The heterozygous c. 661G〉A（E221K） mutation of GCK gene was found in four persons of one pedigree. The proband was diagnosed as MODY2. Impaired glucose regulation was found in two other persons carrying the mutation. The other person also carrying the mutation showed normal blood glucose level. In the other pedigree, there were two members who carried the heterozygous c. 771G〉A（W257ter） mutation of GCK. The proband could be diagnosed with MODY2, the other one was diagnosed with impaired glucose regulation. Restricted diets and enhanced exercises did well in controlling the blood glucose level. Conclusions The c. 661G〉A（E221K） and c. 771G〉A （W257ter） mutations of GCK gene are responsible for the MODY2. The c. 771G〉A（W257ter） mutation of GCK is newly found, the further function study is imperative.

关 键 词：基因 葡萄糖激酶 青少年发病的成年型糖尿病 c.661G〉A(E221K) c.771G〉A(W257ter) 

分 类 号：R587.1[医药卫生—内分泌]