Identification of monogenic gene mutations in Japanese subjects diagnosed with type 1B diabetes between > 5 and 15.1 years of age.

Background: Monogenic mutations, such as those in the potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) and insulin (INS) genes, are identified in young patients with type 1B diabetes (non-autoimmune-mediated). We recently reported the results of a test for monogenic forms of diabetes in Japanese children who were diagnosed with type 1B diabetes at < 5 years of age. In this study, we tested for monogenic forms of diabetes in Japanese children aged > 5 to ≤ 15.1 years at the diagnosis of type 1B diabetes. Methods: Thirty-two Japanese children (eight males, 24 females) with type 1 diabetes negative for glutamate decarboxylase (GAD) 65 and/or IA-2A autoantibodies and who were aged > 5 to 15.1 years at diagnosis were recruited from 16 independent hospitals participating in the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT). We performed mutational analyses of genes with a high frequency of mutation [INS, KCNJ11, hepatocyte nuclear factor 1 alpha (HNF1α) and hepatocyte nuclear factor 4 alpha (HNF4α)]. Results: We identified one missense mutation (G32S) in the INS gene and two mutations (R131Q and R203S) in the HNF1a gene that could be associated with diabetes. No missense change was found in the KCNJ11 gene. Conclusions: Our results suggest that although mutations in the INS gene can be detected in Japanese patients aged > 5 years at diagnosis, the frequency of mutations decrease in older age groups. Conversely, the frequency of the mutation in the HNF1α gene increased in patients diagnosed at age 5 or older. Clinicians should consider the possibility of maturity onset diabetes of the young (MODY) in children diagnosed with type 1B diabetes. [ABSTRACT FROM AUTHOR]