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

✍ Scribed by Issei Yoshiuchi; Kazuya Yamagata; Masaaki Yoshimoto; Qian Zhu; Qin Yang; Takao Nammo; Rikako Uenaka; Ei-ichi Kinoshita; Toshiaki Hanafusa; Jun-ichiro Miyagawa; Yuji Matsuzawa

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 380 KB
• Volume: 18
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1196

✦ Synopsis

Mutations in the transcription factor hepatocyte nuclear factor-1a (HNF-1a; 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 b-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 1a. 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-1a protein. Reporter gene analysis indicated that the mutant HNF-1a had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1a may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345351, 2001.