Recent studies have shown that mutations in the hepatocyte nuclear factor (HNF)-1α gene are the cause of maturity-onset diabetes of the young type 3 (MODY3). We have screened 193 unrelated Japanese subjects with NIDDM for mutations in this gene: 83 with early-onset NIDDM (diagnosis at <30 years of age) and 110 with late-onset NIDDM (diagnosis >30 years of age). All of the members of the latter group also had at least one sibling with NIDDM. The 10 exons, flanking introns, and promoter region were amplified using polymerase chain reaction and were sequenced directly. Mutations were found in 7 of the 83 (8%) unrelated subjects with early-onset NIDDM. The mutations were each different and included four missense mutations (L12H, R131Q, K205Q, and R263C) and three frameshift mutations (P379fsdelCT, T392fsdelA, and L584S585fsinsTC). One of the 110 subjects with late-onset NIDDM was heterozygous for the missense mutation G191D. This subject, who was diagnosed with NIDDM at 64 years of age, also had a brother with NIDDM (age at diagnosis, 54 years) who carried the same mutation, suggesting that this mutation contributed to the development of NIDDM in these two siblings. None of these mutations were present in 50 unrelated subjects with normal glucose tolerance (100 normal chromosomes). Mutations in the HNF-1α gene occur in Japanese subjects with NIDDM and appear to be an important cause of early-onset NIDDM in this population. In addition, they are present in about 1% of subjects with late-onset NIDDM.
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Original Articles|
September 01 1997
Mutations in the Hepatocyte Nuclear Factor-1α/MODY3 Gene in Japanese Subjects With Early- and Late-Onset NIDDM
Naoko Iwasaki;
Naoko Iwasaki
Diabetes Center, Tokyo Women's Medical College
Tokyo, Japan
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Naohisa Oda;
Naohisa Oda
Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago
Chicago, Illinois
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Makiko Ogata;
Makiko Ogata
Diabetes Center, Tokyo Women's Medical College
Tokyo, Japan
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Manami Hara;
Manami Hara
Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago
Chicago, Illinois
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Yoshinori Hinokio;
Yoshinori Hinokio
Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago
Chicago, Illinois
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Yukie Oda;
Yukie Oda
Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago
Chicago, Illinois
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Kazuya Yamagata;
Kazuya Yamagata
Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago
Chicago, Illinois
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Sachiko Kanematsu;
Sachiko Kanematsu
Department of Pediatrics, Tokyo Women's Medical College
Tokyo, Japan
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Hisako Ohgawara;
Hisako Ohgawara
Medical Research Institute, Tokyo Women's Medical College
Tokyo, Japan
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Yasue Omori;
Yasue Omori
Diabetes Center, Tokyo Women's Medical College
Tokyo, Japan
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Graeme I Bell
Graeme I Bell
Howard Hughes Medical Institute and the Departments of Biochemistry and Molecular Biology and Medicine, University of Chicago
Chicago, Illinois
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Address correspondence and reprint requests to Dr. Naoko Iwasaki, Diabetes Center, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.
Diabetes 1997;46(9):1504–1508
Article history
Received:
January 23 1997
Revision Received:
April 14 1997
Accepted:
April 14 1997
PubMed:
9287053
Citation
Naoko Iwasaki, Naohisa Oda, Makiko Ogata, Manami Hara, Yoshinori Hinokio, Yukie Oda, Kazuya Yamagata, Sachiko Kanematsu, Hisako Ohgawara, Yasue Omori, Graeme I Bell; Mutations in the Hepatocyte Nuclear Factor-1α/MODY3 Gene in Japanese Subjects With Early- and Late-Onset NIDDM. Diabetes 1 September 1997; 46 (9): 1504–1508. https://doi.org/10.2337/diab.46.9.1504
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