Introduction and Objective: MODY is estimated to account for 1-2% of all diabetes cases, with HNF1A-MODY being the most common subtype. While most studies have focused on Europe and North America, this study analyzes HNF1A mutation data and examines the clinical characteristics of Asian individuals with HNF1A-MODY.Methods: We collected data from 38 studies on Asian individuals with HNF1A-MODY, comprising a total of 97 probands, sourced from PubMed, Medline, Embase, and Web of Science. The search terms included: “maturity-onset diabetes of the young” or “MODY” or “maturity-onset diabetes of the young type 3” or “MODY3″or “HNF1A-MODY” or “TCF1 mutation”. Both mutations and clinical characteristics were analyzed.Results: A total of 67 distinct amino acid alterations were identified in the HNF1A protein. Among 97 probands, 89 (91.8%) had HNF1A-MODY due to coding region mutations, while 8 (8.2%) had mutations in noncoding regions. The most common mutations were in exons 1 and 4, with missense mutations predominating. In the DNA-binding domain, 67.2% of mutations were missense, while in the transactivation domain, 62.9% were frameshift. Of the probands, 74.2% were diagnosed under 25 years, and 94.8% had a family history of diabetes or hyperglycemia. Age of onset was younger for mutations in the transactivation domain (16.2 years) compared to the DNA-binding domain (20.5 years) and DNA dimerization domain (24.8 years). At diagnosis, 82.5% were normal weight or underweight. Treatment included insulin alone (21.6%), sulfonylureas alone (16.5%), and a sulfonylurea combination (12.4%).Conclusion: In the Asian population, HNF1A-MODY is most caused by missense mutations in the coding region of the HNF1A gene, particularly in exons 1 and 4 of the DNA-binding domain. The age of onset, family history, FBG, HbA1c and BMI may serve as key diagnostic indicators for HNF1A-MODY.
A. Murusuri: None. J. Tang: None.
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