GCK Mutation Analysis and Clinical Profiles of Chinese Pediatric Patients with MODY2: Insights into Screening and Diagnosis

中国儿童MODY2患者的GCK基因突变分析及临床特征:对筛查和诊断的启示

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Abstract

OBJECTIVE: To investigate the clinical and genetic features of maturity onset diabetes of the young type 2 (MODY 2) in Chinese pediatric patients and optimize the screening strategy. METHODS: A total of 11 Chinese pediatric patients diagnosed with MODY2 were enrolled in this study. Detailed clinical data and follow-up outcomes were retrospectively collected and summarized. Genetic testing was conducted using next-generation sequencing (NGS), and all identified variations were verified by Sanger sequencing. RESULTS: All cases carried heterozygous mutations in the GCK gene. 9 pathogenic variations were identified, including 8 missense mutations, 1 frameshift mutation, and 1 splice-site mutation. Among these, the mutation c.456T>G was novel. The mean age at diagnosis was 8.1±2.7 (years). 10 of 11 cases had a family history of hyperglycemia or diabetes. 2 cases were overweight. Patients exhibited mild hyperglycemia. The median HbA1c was 6.3% (interquartile range [IQR]: 6.3%-6.4%). Glucose increment in OGTT was 1.68±0.95 mmol/L. Mean triglyceride level was 0.62±0.15 mmol/L. Two cases were positive for insulin antibodies. All cases were treated with a balanced diet after diagnosis. The follow-up period was 1.5-7 years, and the median HbA1c was 6.3% (IQR: 6.2%-6.4%). CONCLUSION: MODY2 typically manifests with mild, stable fasting hyperglycemia and is predominantly caused by missense mutations in the GCK gene. Our findings support the inclusion of triglyceride levels as a screening marker and highlight that features like overweight status and autoantibody positivity may coexist in MODY2, warranting comprehensive evaluation to prevent misdiagnosis.

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