R127W-HNF-4α is a loss of function mutation but not a rare polymorphism and causes Type II diabetes in a Japanese family with MODY1

Diabetologia

Volumn 43, Issue 4, 2000, Pages 520-524

  Yang, Q ^a   Yamagata, K ^a,d   Yamamoto, K ^b   Cao, Y ^a   Miyagawa, J ^a   Fukamizu, A ^c   Hanafusa, T ^a   Matsuzawa, Y ^a  

^a OSAKA UNIVERSITY   (Japan)

^b OSAKA UNIVERSITY HOSPITAL   (Japan)

^c UNIVERSITY OF TSUKUBA   (Japan)

^d OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

HNF 1 ; HNF 4 ; Insulin; L type pyruvate kinase; MODY

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; DNA; NUCLEAR FACTOR; PYRUVATE KINASE; BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; DNA BINDING PROTEIN; HEPATOCYTE NUCLEAR FACTOR 4; HNF4A PROTEIN, HUMAN; MLX PROTEIN, HUMAN; PHOSPHOPROTEIN; TRANSCRIPTION FACTOR;

ARTICLE; CELLULAR DISTRIBUTION; DNA BINDING; GENE; GENE MUTATION; GENETIC POLYMORPHISM; HUMAN; HUMAN CELL; MATURITY ONSET DIABETES MELLITUS; MISSENSE MUTATION; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; CELL LINE; CELL NUCLEUS; CHEMISTRY; GENETIC TRANSCRIPTION; GENETIC TRANSFECTION; GENETICS; HELA CELL; JAPAN; METABOLISM; MUTATION; PEDIGREE; TRANSACTIVATION;

BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; CELL LINE; CELL NUCLEUS; DIABETES MELLITUS, TYPE 2; DNA; DNA-BINDING PROTEINS; HELA CELLS; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; JAPAN; MUTATION; MUTATION, MISSENSE; PEDIGREE; PHOSPHOPROTEINS; PYRUVATE KINASE; TRANS-ACTIVATION (GENETICS); TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; TRANSFECTION;

EID: 0034166873     PISSN: 0012186X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s001250051338     Document Type: Article

References (10)

1. Yamagata K, Furuta H, Oda N et al. (1996) Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1). Nature 384: 458-460
2. Jiang G, Sladek FM (1997) The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative, specific binding to DNA and heterodimerization with the retinoid X receptor a. J Biol Chem 272: 1218-1225
3. Furuta H, Iwasaki N, Oda N et al. (1997) Organization and partial sequence of the hepatocyte nuclear factor-4α/ MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY Diabetes 46: 1652-1657
4. Yoshida E, Aratani S, Itou H et al. (1997) Functional association between CBP and HNF4 in trans-activation. Biochem Biophys Res Commun 241: 664-669
5. Navas MA, Munoz-Elias EJ, Kim J et al. (1999) Functional characterization of the MODY1 gene mutations HNF4 (R127W), HNF4 (V255M), and HNF4 (E276Q). Diabetes 48: 1459-1465
6. Hadzopoulou-Cladaras M, Kistanova E, Evagelopoulou C et al. (1997) Functional domains of the nuclear receptor hepatocyte nuclear factor 4. J Biol Chem 272: 539-550
7. Yamagata K, Yang Q, Yamamoto K et al. (1998) Mutation P291fsinsC in the transcription factor hepatocyte nuclear factor-1α is dominant negative. Diabetes 47: 1231-1235
8. Stoffel M, Duncan S (1997) The maturity-onset diabetes of the young (MODY1) transcription factor HNF4α regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA 94: 13209-13214
9. Suaud L, Hemimou Y, Formstecher P et al. (1999) Functional study of the E276Q mutant hepatocyte nuclear factor-4α found in type 1 maturity-onset diabetes of the young: Impaired synergy with chicken ovalbumin upstream promoter transcription factor II on the hepatocyte nuclear factor-1 promoter. Diabetes 48: 1162-1167
10. Bell GI, Xiang KS, Newman MV et al. (1991) Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20 q. Proc Natl Acad Sci USA 88: 1484-1488