The list of institutions participating in the JSGIT is given in the Appendix.
Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 yr of age
Article first published online: 10 SEP 2012
© 2012 John Wiley & Sons A/S
Volume 14, Issue 2, pages 112–120, March 2013
How to Cite
The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT). Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 yr of age., , , , , , , , , , , , ,
- Issue published online: 25 FEB 2013
- Article first published online: 10 SEP 2012
- Manuscript Revised: 12 JUL 2012
- Manuscript Accepted: 12 JUL 2012
- Manuscript Received: 31 JAN 2012
- Kawano Masanori Memorial Foundation for the Promotion of Pediatrics
- Japan Society for the Promotion of Science
- Japan Diabetes Foundation
- Ministry of Health, Labour and Welfare
- insulin gene (INS);
- KCNJ11 gene;
- monogenic diabetes;
- type 1B diabetes
The etiology of type 1 diabetes (T1D) is heterogeneous and is according to presence or absence of pancreatic autoantibodies 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.
Thirty four (19 males and 15 female) unrelated Japanese children with glutamate decarboxylase (GAD) 65 antibodies and/or IA-2A-negative T1D and diabetes diagnosed at < 5 yr of age were recruited from 17 unrelated hospitals participating in the Japanese Study Group of Insulin Therapy for children and adolescent diabetes (JSGIT). We screened the INS gene and the KCNJ11 gene which encode the ATP-sensitive potassium cannel by direct sequencing in 34 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 yr of age.