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18p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 18p 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.