单基因糖尿病10例患儿的临床特征与遗传学病因分析  

Clinical characteristics and genetic analysis of children and adolescents with monogenic diabetes

作　　者：方洁[1] 张萍萍[1] 冯跃英 丁曙霞[1] 闫露露[2] 李海波 Fang Jie;Zhang Pingping;Feng Yueying;Ding Shuxia;Yan Lulu;Li Haibo(Department of Pediatrics,Ningbo Women and Children′s Hospital,Ningbo,Zhejiang 315012,China;Central Laboratory for Birth Defects Prevention and Control,Ningbo Women and Children′s Hospital,Ningbo,Zhejiang 315012,China)

机构地区：[1]宁波市妇女儿童医院儿科,宁波315012 [2]宁波市妇女儿童医院出生缺陷综合防治中心,宁波315012

出　　处：《中华医学遗传学杂志》2024年第7期783-789,共7页Chinese Journal of Medical Genetics

基　　金：宁波市社会公益项目(2022S035、202002N3150);宁波市医学品牌学科(PPXK2018-06);宁波市医疗卫生高端团队重大攻坚项目(2022020405);浙江省医药卫生科技计划项目(2023KY290)。

摘　　要：目的探讨10例单基因糖尿病患儿的临床特征与遗传学病因。方法回顾性分析2020年1月至2023年3月宁波市妇女儿童医院收治的116例糖尿病患儿的临床资料及实验室检查数据,进行糖尿病分型,对其中21例疑诊为单基因糖尿病的患儿进行全外显子组测序(WES)及线粒体基因测序。结果共发现10例单基因糖尿病患儿,均为青少年起病的成人型糖尿病(MODY),其中6例为GCK基因变异所致的MODY2,1例为HNF1A基因变异所致的MODY3,2例为ABCC8基因变异所致的MODY12,1例为KCNJ11基因变异所致的MODY13。10例患儿中仅1例因"多饮多尿"就诊,其他均无典型的糖尿病症状。MODY组的糖尿病家族史阳性率显著高于1型糖尿病(T1DM)组及2型糖尿病(T2DM)组(P<0.05)。MODY组的BMI较T1DM组高(P<0.05),初诊血糖较T1DM组低(P<0.05),空腹C肽水平较T1DM组高(P<0.05),糖化血红蛋白较T1DM组、T2DM组均低(P<0.05)。结论本研究纳入的患儿中,单基因糖尿病以MODY最常见,GCK基因变异所致的MODY2占主要类型。MODY患儿初诊血糖及糖化血红蛋白轻度升高,胰岛细胞功能尚存,临床表现及实验室检查与T2DM患儿存在重叠。WES联合线粒体基因测序可望明确单基因糖尿病的病因学诊断,有助于实现精准治疗。Objective To explore the clinical characteristics and molecular basis for children and adolescents with monogenic diabetes.Methods A retrospective analysis was carried out for the clinical manifestations and laboratory data of 116 children and adolescents diagnosed with diabetes at Ningbo Women and Children′s Hospital from January 2020 to March 2023.Whole exome sequencing and mitochondrial gene sequencing were carried out on 21 children with suspected monogenic diabetes.Results A total of 10 cases of monogenic diabetes were diagnosed,all of which were Maturity-onset Diabetes Of the Young(MODY).Six cases of MODY2 were due to GCK gene mutations,1 case of MODY3 was due to HNF1A gene mutation,2 cases of MODY12 were due to ABCC8 gene mutations,and 1 case of MODY13 was due to KCNJ11 gene mutation.Nine of the 10 patients with MODY had no typical symptoms of diabetes.A family history of diabetes was significantly more common in the MODY group compared with the T1DM and T2DM groups(P<0.05).The BMI of the MODY group was higher than that of the T1DM group(P<0.05).The initial blood glucose level was lower than that of the T1DM group(P<0.05),and there was no significant difference compared with the T2DM group.The fasting C-peptide level of the MODY group was higher than that of the T1DM group(P<0.05),and there was no significant difference compared with the T2DM group.Glycosylated hemoglobin of the MODY group was lower than both the T1DM and T2DM groups(P<0.05).Conclusion In this study,MODY has accounted for the majority of monogenic diabetes among children and adolescents,and the common mutations were those of the GCK gene in association with MODY2.Blood glucose and glycosylated hemoglobin of children with MODY were slightly increased,whilst the islet cell function had remained,and the clinical manifestations and laboratory tests had overlapped with those of type 2 diabetes.WES and mitochondrial gene sequencing can clarify the etiology of monogenic diabetes and facilitate precise treatment.

关 键 词：全外显子组测序 线粒体基因测序 单基因糖尿病 青少年起病的成人型糖尿病 

分 类 号：R725.8[医药卫生—儿科]