Analysis of a non-functional HNF-1α (TCF1) mutation in Japanese subjects with familial type 1 diabetes
Mutations in the transcription factor hepatocyte nuclear factor‐1α (HNF‐1α; gene symbol TCF1) cause maturity‐onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic β‐cell dysfunction. Recent genetic studies...
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| Published in | Human mutation Vol. 18; no. 4; pp. 345 - 351 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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New York
John Wiley & Sons, Inc
01.10.2001
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| Abstract | Mutations in the transcription factor hepatocyte nuclear factor‐1α (HNF‐1α; gene symbol TCF1) cause maturity‐onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic β‐cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non‐autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1α. The expression of the mutant protein was not detected in COS‐7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF‐1α protein. Reporter gene analysis indicated that the mutant HNF‐1α had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF‐1α may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345–351, 2001. © 2001 Wiley‐Liss, Inc. |
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| AbstractList | Mutations in the transcription factor hepatocyte nuclear factor‐1α (HNF‐1α; gene symbol TCF1) cause maturity‐onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic β‐cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non‐autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1α. The expression of the mutant protein was not detected in COS‐7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF‐1α protein. Reporter gene analysis indicated that the mutant HNF‐1α had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF‐1α may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345–351, 2001. © 2001 Wiley‐Liss, Inc. |
| Author | Zhu, Qian Matsuzawa, Yuji Nammo, Takao Miyagawa, Jun-ichiro Yoshiuchi, Issei Yoshimoto, Masaaki Hanafusa, Toshiaki Yang, Qin Kinoshita, Ei-ichi Uenaka, Rikako Yamagata, Kazuya |
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| Notes | Japanese Ministry of Science, Education and Culture Japan Insulin Study Group Japanese Ministry of Health and Welfare (Health Science Research Grants; Research on Human Genome and Gene Therapy) Research for Future Program of Japan Society for the Promotion of Science - No. 97L00801 istex:85F491B49D0AF200DB74A452DC2E3FF409163A61 ArticleID:HUMU1196 Yamanouchi Foundation for Research on Metabolic Disorders ark:/67375/WNG-MMSQP6B2-4 |
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| SubjectTerms | diabetes diabetes, type 1 hepatocyte nuclear factor-1α HNF-1α maturity-onset diabetes of the young MODY3 TCF1 type 1 |
| Title | Analysis of a non-functional HNF-1α (TCF1) mutation in Japanese subjects with familial type 1 diabetes |
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