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Analysis of a non‐functional HNF‐1α (TCF1) mutation in Japanese subjects with familial type 1 diabetes
Author(s) -
Yoshiuchi Issei,
Yamagata Kazuya,
Yoshimoto Masaaki,
Zhu Qian,
Yang Qin,
Nammo Takao,
Uenaka Rikako,
Kinoshita Eiichi,
Hanafusa Toshiaki,
Miyagawa Junichiro,
Matsuzawa Yuji
Publication year - 2001
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1196
Subject(s) - biology , tcf7l2 , haploinsufficiency , frameshift mutation , hnf1a , transactivation , mutant , maturity onset diabetes of the young , genetics , mutation , gene , transcription factor , phenotype , genotype , single nucleotide polymorphism
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.