青少年发病的成人型糖尿病2型的临床与分子遗传学研究

Clinical and molecular features in Maturity-onset diabetes of the young type 2

目的探讨青少年发病的成人型糖尿病2型(maturity-onset diabetes of the young type 2,MODY2)的临床特征及GCK基因变异类型特点,分析GCK基因型与临床表型的关系。方法分析2011年4月至2021年10月在广州市妇女儿童医疗中心内分泌科临床诊断为MODY2的32例患儿临床资料,并进行GCK基因Sanger测序及家系调查,对未检出GCK基因变异的患儿父母亲进行全外显子检测,分析其分子遗传学特征。结果32例患儿(男19例,女13例),起病年龄1 d~18岁,中位数为8岁,空腹血糖均轻度升高,均值(6.7±0.6)mmol/L,糖化血红蛋白均值(5.90±0.96)%,均无高血糖症状。31例患儿随访4~75个月血糖维持稳定。32例患儿共发现GCK基因30个不同杂合变异,其中5例为新发变异,2例患儿为自发变异。结论MODY2患儿轻度高血糖生后即可出现,不同的GCK基因变异所导致的临床表型无明显差异,无家族史但临床高度提示MODY2的患儿也应行GCK基因分析,以免造成漏诊,并对家系相关成员进行筛查,有助于优化治疗方案,本组研究未发现GCK基因热点变异。

Objective Toinvestigate the clinical phenotype and molecular genetic characteristics of Maturityonset diabetes of the youngtype 2(MOYD2),and to explore the correlations between GCK genotype and clinical phenotypes.Methods From April 2011 to October 2021,clinical data of 32 children diagnosed with MODY2 in Department of Endocrinology of Guangzhou Women and Children′s Medical Center were collected.Sanger sequencing and family investigation for GCK gene were conducted.Parents of the children without GCK gene variation were assayed for the whole exon profile and their molecular genetic characteristics were analyzed in depth.Results A total of 32 children(male=19 and female=13)with the onset age ranging from 1-day to 18-year old were included and the medium value was approximately 8-year old.Fasting blood glucose was slightly elevated in all patients,with mean value of(6.7±0.6)mmol/L,and the mean value of HbA1c was(5.9±0.96%).All patients didn′t present the symptoms caused by hyperglycemia.The levels of blood glucose in the 31 patients remained stable during the follow-up 4 months till 75 months.A total of 30 different heterozygous variants were found in the 32 children,including 5 new variants and 2 spontaneous variants.Conclusions Mild hyperglycemia occurred in children withMODY2 after birthand there was no significant difference for the clinical phenotypes caused by different GCK gene variations.Children with no family history but highly suggestive of MODY2 should undergo GCK gene sequencing to avoid missed diagnosis,and relevant family members should be screened to aid the optimization of treatment plan.No hot spot variation of GCK gene was found in this study.