Abstract
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 HNF1α 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.
Acknowledgments
We sincerely thank the JSGIT for providing the resources to conduct this study, as well as the participating patients and their families. We also thank the physicians and pediatricians who collected the blood samples and clinical/biological data.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science, by the Japan Diabetes Foundation, and by Health Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare (for neonatal diabetes mellitus).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Appendix
The JSGIT comprises the following institutions:
Koji Takemoto, Ehime University; Shigeyuki Ohtsu, Kitasato University; Kohji Tsubouchi, Chuno Kosei Hospital;
Kisho Kobayashi, Yamanashi University; Akemi Koike, Koike Child Clinic; Takahiro Mochizuki, Osaka Police Hospital;
Kanshi Minamitani, Teikyo University Chiba Medical Center;
Ryuzo Takaya, Osaka Medical College; Hiroshi Mochizuki, Katsuya Aizu, Saitama Children’s Medical Center;
Zenro Kizaki, Japanese Red Cross Kyoto Daiichi Hospital; Tetsuo Mori, Nagano Red Cross Hospital;
Naoto Shimura, Dokkyo Medical University; Tokuo Mukai, Asahikawa-Kosei General Hospital; Nobuo Matsuura, Teine Keijinkai Hospital;
Takao Fujisawa, National Mie Hospital; Kenji Ihara, Kyushu University; Kitaro Kosaka, Kyoto Prefectural University of Medicine;
Rika Kizu, Yokosuka Kyosai Hospital; Toshikazu Takahashi, Takahashi Clinic; Satoshi Matsuo, Matsuo Child Clinic;
Keiichi Hanaki, Tottori Prefectural Kousei Hospital; Yutaka Igarashi, Igarashi Children’s Clinic;
Goro Sasaki, Tokyo Dental College Ichikawa General Hospital; Shun Soneda, St. Marianna University;
Shinichi Teno, Teno Clinic; Susumu Kanzaki, Tottori University; Ikuko Takahashi, Akita University;
Yusuke Tanahashi, Asahikawa Medical University; Akira Endo, Iwata City Hpspital; Mahoko Hurujyo, Okayama Medical Center;
Yoshiya Ito, Kitami Red Cross Hospital; Tomohiro Hori, Gifu University; Yasusada Kawata, Kyushyu Rosai Hospital;
Hisakazu Nakajima, Kyoto Prefectural University of Medicine; Yukiyo Yamamoto, University of Occupational and Environmental Health;
Hiroko Kadowaki, Sanno Hospital; Hiroki Matsuura, Shinshyu University; Eishin Ogawa, Teikyo University;
Emiko Tachikawa, Tokyo Women’s Medical University; Kaori Sasaki, Tokyo Women’s Medical University Yachiyo Medical Center;
Junichi Nagaishi, Tottori Municipal Hospital; Junko Ito, Toranomon Hospital; Yohei Ogawa, Niigata University;
Shinnji Kadoya, Nishinomiya Municipal Central Hospital; Shoji Nakayama, Mominoki Hospital;
Jyunichi Arai, Hosogi Hospital; Kentaro Shiga, Yokohama City University Medical Center.
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