Molecular analyses of Japanese patients with neonatal/infantile diabetes mellitus.

• Project/Area Number: 17591084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: YORIHUJI Tohru Kyoto University, Graduate School of Medicine, instructor, 医学研究科, 講師 (60220779)
• Co-Investigator(Kenkyū-buntansha): KAWAI Masahiko Kyoto University, Graduate School of Medicine, assistant professor, 医学研究科, 助手 (00283599)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: neonatal diabetes mellitus / infantile diabetes mellitus / childhood diabetes mellitus / Kir6.2 (KCNJ11)

Research Abstract

We analyzed a Japanese family with dominantly inherited diabetes mellitus including transient neonatal diabetes, childhood diabetes, gestational diabetes, and adult-onset type 2 diabetes. We found a novel C42R mutation in the KCNJ 11 gene segregating with the diabetic phenotype. Electrophysiological studies indicated that the open probabilities of the mutant channels are higher than those of wild type channels. These results indicate that the KCNJ11 gene is a part of MODY genes among Japanese. We then analyzed 35 different Japanese families with dominantly inherited diabetes, and found an additional 4 families with KCNJ11 mutations. One of the family members in these families had the onset of diabetes at 18 years of age further indicating the importance of this gene as an etiology of adult-onset diabetes.
We then performed mutational analyses on 35 Japanese families with child-onset diabetes mellitus and identified causative mutations in 11 families including three families with GCK mutations, one with HNF4A, four with KCNJ11, three with TCF1, and one with TCF2.

Research Products

• [Journal Article] Fibrilline I gene polymorphism is associated with tall stature of normal individuals. (2007)
  • Author(s): Mamada M, Yorifuji T et al.
  • Journal Title: Hum Genet 120 Pages: 733-733
• [Journal Article] Prevalence of mutations in the FGFR3 gene In individuals with idiopathic short stature (2006)
  • Author(s): Mamada M, Yorifuji T et al.
  • Journal Title: Clin Pediatr Endocrinol 15 Pages: 61-61
  • NAID: 130004430987
• [Journal Article] Effects of arginine treatment on nutrition, growth, and urea cycle function in seven Japanese patients with late onset ornithine transcarbamylase deficiency (2006)
  • Author(s): Nagasaka H, Yorifuji T et al.
  • Journal Title: Eur J Pediatr 165 Pages: 618-618
• [Journal Article] The C42R mutation In the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes mellitus, childhood diabetes, or later-onset apparently type 2 diabetes mellitus. (2005)
  • Author(s): Yorifuji T et al.
  • Journal Title: J Clin Endocrinol Metab 90巻 Pages: 3174-3178
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The C42R mutation In the Kir6.2 (KCNJ 11) gene as a cause of transient neonatal diabetes mellitus, childhood diabetes, or later-onset apparently type 2 diabetes mellitus. (2005)
  • Author(s): Yorifuji T et al.
  • Journal Title: J Clin Endocrinol Metab 90 Pages: 3174-3178
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The C42R mutation in the Kir6.2(KCNJ11)gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type2 diabetes mellitus (2005)
  • Author(s): Yorifuji T
  • Journal Title: Journal of Clinical Endocrinology and Metabolism 90 Pages: 3174-3178