Identification of genetic factor for type 1 diabetes mellitus

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The etiology of type 1 diabetes (T1D) is heterogeneous and is according to presence or absence of pancreatic auto antibodies divided into two subtypes: type 1A (autoimmune-mediated) and type 1B (non-autoimmune-mediated). Although several genes have been linked to type 1A diabetes, the genetic cause of type 1B diabetes in Japanese individuals is far from understood. The aim of this study was to test for monogenic forms of diabetes in auto antibody-negative Japanese children with T1D. We identified three novel (C31Y, C96R and C109F) mutations and one previously reported mutation (R89C) in the INS gene in five children, in addition to one mutation in the KCNJ11 gene (H46R) in one child. These mutations are most likely pathogenic and therefore the cause of diabetes in carriers. Our results suggest that monogenic forms of diabetes, particularly INS gene mutations, can be detected in Japanese patients classified with type 1B. Mutation screening, at least of the INS gene, is recommended for Japanese patients diagnosed as autoantibody negative at < 5 years of age. Genetic testing is recommended in all patients diagnosed with diabetes before 6 months of age. Further studies in other patients with type 1B diabetes and their families are needed to elucidate the contributions of mutations to the T1D phenotype.