目的：对中国人群MODY（maturity onset diabetes of the young)的临床特征及遗传发病机制进行探讨。方法：回顾性分析2018年9月至2021年3月于南京鼓楼医院内分泌科就诊并疑诊为MODY的49例患者，收集临床及实验室资料，应用MODY概率计算器（MODY probability calculator，MPC）计算MODY可能性，取得知情同意后留取患者血液标本进行二代测序并家系验证，根据ACMG (The American College of Medical Genetics and Genomics)指南解读突变性质。根据基因检测结果及致病性评估结果分为MODY组及非MODY组，回顾性收集患者一般资料及血糖控制、胰岛功能、血脂代谢、并发症、发生酮症情况等指标，使用SPSS 26.0 统计软件进行数据处理，分析各组间在上述方面有无差异。结果：16例患者分别为：一例HNF4α-MODY 合并先天性胰腺发育不良、一例GCK-MODY，三例HNF1α-MODY 、五例ABCC8-MODY、两例PAX4-MODY 、一例PAX4-MODY合并KCNJ11-MODY、一例NEUROD1-MODY 、二例INS-MODY。其中女性占62.5%，平均起病年龄为20.75岁，平均体质指数（BMI）为22.18kg/m2，7例（43.7%）患者出现过酮症，3例患者无糖尿病家族史，仅4例患者有三代糖尿病家族史，达MODY临床诊断标准的患者仅1例，在并发症方面，1例同时合并糖尿病肾病及糖尿病周围神经病变，共2例患者出现糖尿病视网膜病变，2例患者存在糖尿病周围神经病变，2例患者出现动脉粥样硬化伴斑块形成，这两例患者目前无血脂代谢紊乱，未出现心血管事件。MODY组及非MODY组在血糖控制、胰岛功能、血脂代谢及并发症发面无显著差异，MODY组发生酮症比例更高，P<0.05。应用MPC计算，MODY组6例患者阳性预测率(Positive prediction rate,PPV)＞62.4%(P=0.949)，诊断敏感性为 35.3%，特异性为 68.8%，阳性预测值为37.5 %，阴性预测值为66.7%。结论：1、MODY患者临床特征呈显著异质性：MODY患者可合并多个基因突变，同一基因可合并多个突变；同一MODY亚型临床特征、疾病转归、并发症发生发展情况可大不相同；MODY患者可合并器官发育不良。2、相比于非MODY组，MODY组酮症起病比例更高，但在其他临床特征上差异不明显；3、中国人群中ABCC8可能为常见致病基因； 4、MPC在中国人群MODY筛查中的应用稍局限。

Objective: The aim of this study was to investigate the clinical characteristics and genetic pathogenesis of MODY (maturity onset diabetes of the young) in Chinese population. 

Methods: Clinical and laboratory data of 49 cases were collected, and MODY probability calculator (MPC) was used to evaluate the possibility of MODY，a panel of monogenic diabetes related genes were screened and pathogenicity of the variants were assessed by bioinformatics prediction software programs and segregation analyses. These cases were divided into MODY group and non-MODY group according to the results of genetic testing and pathogenicity assessment, SPSS 26.0 statistical software was used to analyze their characteristics.

Results: Mutations were found in 19/49 participants, among which 16 were pathogenic/likely pathogenic variants. Females accounted for 62.5%, the average age of onset was 20.75 years, the average body mass index was 22.18kg/m2, 7 patients (43.7%) had ketosis. In terms of complications, 1 patient got both nephropathy and peripheral neuropathy, a total of 2 patients got retinopathy, and 2 patients got peripheral nerves. There was no significant difference between the MODY group and the non-MODY group in clinical characters except the rate of ketosis, the MODY group had a higher rate of ketosis, P<0.05. The positive prediction rate (PPV) calculated by MPC of 6 patients in the MODY group was 62.4% (P=0.949,sensitivity 35.3%, specificity 68.8%, positive predictive value 37.5%, negative prediction value 66.7%).

Conclusions: Our study shows heterogeneous in the clinical characteristics of MODY patients. What’s more, compared with non-MODY patient, participants with MODY had a higher incidence of ketosis. We also found that ABCC8 may be a common pathogenic gene leads to MODY in the Chinese population, and the application of MPC in Chinese didn’t show excellent sensitivity and specificity.