Wen Qian, Li Yuwen, Shao Huige, Ma Jun, Lin Yi, Sun Yihu, Liu Ting
Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China.
Department of Endocrinology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, 410004, China.
Open Med (Wars). 2023 May 12;18(1):20230705. doi: 10.1515/med-2023-0705. eCollection 2023.
Maturity-onset diabetes of the young type 3 (MODY3) is a specific type of diabetes mellitus with inherited impairment of the islet β cell function due to the mutation in the hepatocyte nuclear factor 1α (HNF1α) gene. It is a rare condition and easily misdiagnosed as T1DM or T2DM. In this study, the clinical features of two unrelated Chinese MODY3 probands were described and analyzed. Next-generation sequencing was performed to identify the mutated genes, and Sanger sequencing was employed to verify the location of the pathogenic variant in the related family members. It was found that proband 1 inherited a start codon mutation c.2T>C (p.Met1?) in exon 1 of the HNF1α gene from his affected mother, and proband 2 inherited a frameshift mutation c.1136_1137del (p.Pro379fs) in exon 6 of the HNF1α gene also from her affected mother. Proband 1 and proband 2 differed in islet dysfunction, complications, and treatments due to their different disease durations and levels of hemoglobin A (HbA1c). The findings of this study demonstrate that early identification of MODY and diagnosis through genetic testing are critical for the treatment of the patient.
青年发病的成年型糖尿病3型（MODY3）是一种特殊类型的糖尿病，由于肝细胞核因子1α（HNF1α）基因突变导致胰岛β细胞功能遗传性受损。它是一种罕见疾病，容易被误诊为1型糖尿病（T1DM）或2型糖尿病（T2DM）。在本研究中，对两名无血缘关系的中国MODY3先证者的临床特征进行了描述和分析。采用二代测序鉴定突变基因，并用桑格测序法验证相关家庭成员中致病变异的位置。结果发现，先证者1从患病母亲那里继承了HNF1α基因外显子1中的起始密码子突变c.2T>C（p.Met1?），先证者2也从患病母亲那里继承了HNF1α基因外显子6中的移码突变c.1136_1137del（p.Pro379fs）。由于病程和糖化血红蛋白（HbA1c）水平不同，先证者1和先证者2在胰岛功能障碍、并发症及治疗方面存在差异。本研究结果表明，早期识别MODY并通过基因检测进行诊断对患者治疗至关重要。
