Analysis of a non-functional HNF-1? (TCF1) mutation in Japanese subjects with familial type 1 diabetes

• Published in: Human mutation Vol. 18; no. 4; pp. 345 - 351
• Main Authors: Yoshiuchi, Issei, Yamagata, Kazuya, Yoshimoto, Masaaki, Zhu, Qian, Yang, Qin, Nammo, Takao, Uenaka, Rikako, Kinoshita, Ei-ichi, Hanafusa, Toshiaki, Miyagawa, Jun-ichiro, Matsuzawa, Yuji
• Format: Journal Article
• Language: English
• Published: Hoboken Hindawi Limited 01.10.2001
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/humu.1196

Mutations in the transcription factor hepatocyte nuclear factor-1± (HNF-1±; 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 ²-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 1±. 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-1± protein. Reporter gene analysis indicated that the mutant HNF-1± had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1± may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345-351, 2001. © 2001 Wiley-Liss, Inc.