Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor‐1α genes in patients with early‐onset Type 2 diabetes mellitus/MODY

Summary Aims To examine the prevalence of identified MODY‐related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes. Methods Ninety‐two unrelated Chinese subjects with diabetes diagnosed before the age of 40 years who had a positive family history of diabetes were screened for mutations in hepatocyte nuclear factors (HNF‐1α and HNF‐4α) and glucokinase genes by direct sequencing. The family members of patients with mutations and 100 healthy controls were also examined. Results Mutations in the HNF‐1α and the glucokinase genes were found in 5% and 3% of the diabetic subjects, respectively but no mutations were found in the coding region of the HNF‐4α gene. Three mutations found in the glucokinase gene were novel missense mutations (I110T, A119D and G385V). The mutations in the HNF‐1α gene were also new and included four missense mutations (G20R, R203H, S432C, I618M) and one splice acceptor site mutation (IVS2nt‐1G→A). Patients with mutations in these genes were clinically heterogeneous with respect to phenotype and basal pancreat