一个葡萄糖激酶基因Gly162Asp错义突变致青少年发病的成年型糖尿病2型家系报告

摘要

目的 对一个高度怀疑青少年发病的成年型糖尿病2型(MODY2),即葡萄糖激酶(GCK)基因突变所致MODY家系寻找基因突变位点,并探讨其临床特点. 方法对1例意外发现血糖升高、无酮症倾向、有糖尿病家族史的10岁女孩采用芯片捕获高通量测序方法进行致病基因检测,发现其携带GCK基因突变,对其家系进行调查,收集家系成员相关临床资料并取得家系成员的外周血基因组DNA,使用Sanger测序技术对家系成员进行筛查. 结果 该家系的5名成员检测到GCK基因(NM_000162)第5号外显子c.485G>A(p.Gly162Asp) 杂合错义突变,其中有4例为糖尿病患者,1例为IGR,该突变与糖尿病和IGR共分离,在白种人群中已有报道,在中国人群中为首次发现. 结论 GCK基因突变c.485G>A是该MODY2家系的主要致病基因.%Objective To investigate the pathogenic gene and describe the clinical features of maturity-onset diabetes of the young type 2(MODY2)pedigree caused by a glucokinase (GCK) gene mutation.Methods A 10-year-old girl was accidentally found hyperglycemia,with no ketosis tendency.She had a strong family history of diabetes.The pathogenic gene in the proband was detected by chip capture high-throughput sequencing method,and she was found to carry GCK gene mutation.Then,her family was investigated for,clinical data and DNA,screening by Sanger sequencing.Results A heterozygous mutation in GCK gene (NM_000162 ) located in the exon 5 (c.485G>A;p.Gly162Asp) was identified in five members of the pedigree.After the genetic diagnosis of the MODY2,four of them were diagnosed with diabetes and one was impaired glucose regulation.The mutation was cosegregated with diabetes and impaired glucose regulation.This gene mutation has been reported in the white population,but the first time in the Chinese population.Conclusion GCK gene c.485G>A mutation may be linked to this MODY2 pedigree.