儿童糖尿病临床与分子遗传学病因分析  

Phenotype and genetic characteristics of diabetes mellitus in children

作　　者：张开创 梁黎黎[1] 张惠文[1] 王瑞芳[1] 杨奕[1] 孙宇宁 韩连书[1] 余永国[1] 邱文娟[1] ZHANG Kaichuang;LIANG Lili;ZHANG Huiwen;WANG Ruifang;YANG Yi;SUN Yuning;HAN Lianshu;YU Yongguo;QIU Wenjuan(Department of Pediatric Endocrinology and Genetic Metabolism,Shanghai Institute for Pediatric Research,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院上海市儿科医学研究所儿内分泌遗传代谢科,上海200092

出　　处：《临床儿科杂志》2022年第5期345-348,375,共5页Journal of Clinical Pediatrics

基　　金：上海市卫健委面上项目(No.201940226);上海交通大学医学院儿科学院先天性肾上腺皮质功能不全临床研究中心(No.ELYZX202106)。

摘　　要：目的明确儿童单基因糖尿病的临床特点和分子遗传学病因。方法回顾性分析2020年8月至2021年12月收治的76例糖尿病患儿的临床表现和初诊时实验室检查。按照儿童糖尿病分型,分为青少年的成人起病型糖尿病(MODY)组(n=7)、2型糖尿病(T2DM)组(n=7)和1型糖尿病(T1DM)组(n=62)。对其中21例疑似单基因糖尿病患儿行全外显子测序(WES)。结果WES共发现7例单基因糖尿病,均为青少年的成人起病型糖尿病(MODY),3例为GCK变异所致MODY2,3例为HNF1A变异所致MODY3,1例为INS变异所致MODY10。共发现2种未见报道新变异:GCK的c.1124T>G(p.V375G),INS的c.110A>T(p.E37V)变异。7例中5例MODY患儿起病时无典型糖尿病症状,以偶然发现血糖升高入院。MODY组、T2DM组和T1DM组间初诊时空腹血糖、C肽、胰岛素、HbA1c差异均有统计学意义(P<0.05)。MODY组血糖及糖化血红蛋白较T1DM组降低;C肽水平较T1DM组升高,较T2DM组降低;胰岛素水平低于T1DM组和T2DM组,差异均有统计学意义(P<0.05)。1例智力发育落后的T1DM患儿WES检测发现其合并18 p缺失综合征,另1例肝酶进行性升高的T2DM患儿发现其合并Wilson病。结论单基因糖尿病以MODY常见,扩展了MODY的基因变异谱。当儿童糖尿病伴发胰腺外表现时,需考虑合并其他遗传性疾病。Objective Objective To determine phenotype and genetic characteristics of monogenic diabetes in children.Methods Clinical manifestations and laboratory data at initial diagnosis of 76 children with diabetes admitted to our department from August 2020 to December 2021 were retrospectively analyzed.Whole exome sequencing was performed in 21 patients with suspected monogenic diabetes.Results A total of seven cases of monogenic diabetes were identified by whole exome sequencing(WES),all of which were maturity-onset diabetes of the young(MODY).Three cases of MODY2 were caused by GCK variants,and three cases of MODY3 were caused by HNF1A variants and one case of MODY10 caused by INS variant.Two novel variants were identified,including c.1124T>G(p.V375G)in GCK and c.110A>T(p.E37V)in INS.Five of the 7 patients(5/7)with MODY had no typical symptoms of diabetes and were admitted to the hospital due to incidentally elevated glucose level.The level of blood glucose and glycosylated hemoglobin in the MODY group(n=7)were lower than those in the T1DM group(n=62)(P<0.05),and showed no significant difference compared with those of T2DM group(n=7).The levels of insulin and C-peptide in the MODY group were higher than those in the T1DM group(P<0.05),and were significantly lower than those in the T2DM group(P<0.05).In addition,a T1DM child with retarded mental development received an additional diagnosis of 18 p deletion syndrome by WES,and another T2DM child with sustained elevated liver aminotransferase received an additional diagnosis of Wilson Disease by WES.Conclusions MODY is the common type of monogenic diabetes.This study expands the mutation spectrum of MODY.When diabetes patient present with extra-pancreatic manifestations,the combination of other genetic disorders should be considered.

关 键 词：全外显子测序 单基因糖尿病 青少年的成人起病型糖尿病 

分 类 号：R725.8[医药卫生—儿科]