Identification of mutations in the hepatocyte nuclear factor (HNF)-1α gene in Japanese subjects with IDDM

S. Yamada, H. Nishigori, H. Onda, T. Utsugi, T. Yanagawa, T. Maruyama, K. Onigata, K. Nagashima, R. Nagai, A. Morikawa, T. Takeuchi, J. Takeda

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61 Citations (Scopus)


One form of maturity-onset diabetes of the young, MODY3, is characterized by a severe insulin secretory defect, compared with MODY2, a glucokinase-deficient diabetes. It has recently been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor (HNF)- 1α cause MODY3. Because of the rapid progress to overt diabetes and the high prevalence of required insulin treatment in patients with MODY3, we screened the HNF-1α gene for mutations in Japanese subjects with IDDM. Ten exons and flanking introns of the HNF-1α gene in these subjects were amplified by polymerase chain reaction and direct sequencing of the products. Mutations were identified in three (5.5%) of the 55 unrelated subjects with IDDM. A missense mutation of R272H (replacement of Arg by His in codon 272) in the DNA binding domain of HNF-1α was found in a subject who developed IDDM 1 year after diagnosis of NIDDM at 8 years of age. A frameshift mutation of P291fsinsC (insertion of a C in a polyC tract around codon 291 for Pro), which would generate a mutant truncated protein of 340 amino acids, was found in a subject who started insulin treatment when hyperglycemia and ketonuria were noticed at 13 years of age. A missense mutation of R583G (replacement of Arg by Gly in codon 583) in the transactivation domain of HNF-1α was found in a subject with sudden-onset IDDM at 20 years of age. None of these mutations were present in 100 nondiabetic subjects (200 normal chromosomes). These results indicate that the HNF-1α gene defects could lead to the development of not only early-onset NIDDM but also IDDM, implicating the importance of subclassification of HNF-1α-deficient IDDM from a classical type of autoimmune-based IDDM in Japanese.

Original languageEnglish
Pages (from-to)1643-1647
Number of pages5
Issue number10
Publication statusPublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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