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Maturity-onset diabetes of the young, type 1; MODY1

Disease ID:594
Name:Maturity-onset diabetes of the young, type 1; MODY1
Associated with:1 target
Maturity-onset diabetes of the young | MODY
Database Links
Disease Ontology: DOID:0050524
OMIM: 125850, 606391
Orphanet: ORPHA552


Hepatocyte nuclear factor-4-α
Comments:  Mutations in several different human populations affecting either the DNA-binding domain (DBD) or ligand binding domain (LBD) are associated with MODY 1 (phe75fs stop at 117; lys99fs stop at 122; gly115ser; arg125trp; arg127trp; arg154stop; arg244gln; gln268stop; arg324his; val328-329ins; ivs5-2delA). There is also a report of a mutation in the IPF-1 (MODY4) site at -146 in the P2 promoter associated with MODY1.
References:  1,5,8,10-12
Mutations:  Hepatocyte nuclear factor-4-α is associated with 10 mutation. Click here for details


No ligand related data available for Maturity-onset diabetes of the young, type 1; MODY1


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1. Barrio R, Bellanné-Chantelot C, Moreno JC, Morel V, Calle H, Alonso M, Mustieles C. (2002) Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families. J Clin Endocrinol Metab, 87 (6): 2532-9. [PMID:12050210]

2. Furuta H, Iwasaki N, Oda N, Hinokio Y, Horikawa Y, Yamagata K, Yano N, Sugahiro J, Ogata M, Ohgawara H et al.. (1997) Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY. Diabetes, 46 (10): 1652-7. [PMID:9313765]

3. Lausen J, Thomas H, Lemm I, Bulman M, Borgschulze M, Lingott A, Hattersley AT, Ryffel GU. (2000) Naturally occurring mutations in the human HNF4alpha gene impair the function of the transcription factor to a varying degree. Nucleic Acids Res, 28 (2): 430-7. [PMID:10606640]

4. Lehto M, Bitzén PO, Isomaa B, Wipemo C, Wessman Y, Forsblom C, Tuomi T, Taskinen MR, Groop L. (1999) Mutation in the HNF-4alpha gene affects insulin secretion and triglyceride metabolism. Diabetes, 48 (2): 423-5. [PMID:10334325]

5. Monney CT, Kaltenrieder V, Cousin P, Bonny C, Schorderet DF. (2002) Large Family With Maturity-Onset Diabetes of the Young and a Novel V121I Mutation in HNF4A. Hum Mutat, 20 (3): 230-1. [PMID:12203996]

6. Møller AM, Dalgaard LT, Ambye L, Hansen L, Schmitz O, Hansen T, Pedersen O. (1999) A novel Phe75fsdelT mutation in the hepatocyte nuclear factor-4alpha gene in a Danish pedigree with maturity-onset diabetes of the young. J Clin Endocrinol Metab, 84 (1): 367-9. [PMID:9920109]

7. Oxombre B, Kouach M, Moerman E, Formstecher P, Laine B. (2004) The G115S mutation associated with maturity-onset diabetes of the young impairs hepatocyte nuclear factor 4alpha activities and introduces a PKA phosphorylation site in its DNA-binding domain. Biochem J, 383 (Pt. 3): 573-80. [PMID:15233628]

8. Oxombre B, Moerman E, Eeckhoute J, Formstecher P, Laine B. (2002) Mutations in hepatocyte nuclear factor 4alpha (HNF4alpha) gene associated with diabetes result in greater loss of HNF4alpha function in pancreatic beta-cells than in nonpancreatic beta-cells and in reduced activation of the apolipoprotein CIII promoter in hepatic cells. J Mol Med, 80 (7): 423-30. [PMID:12110948]

9. Price JA, Fossey SC, Sale MM, Brewer CS, Freedman BI, Wuerth JP, Bowden DW. (2000) Analysis of the HNF4 alpha gene in Caucasian type II diabetic nephropathic patients. Diabetologia, 43 (3): 364-72. [PMID:10768098]

10. Pruhova S, Ek J, Lebl J, Sumnik Z, Saudek F, Andel M, Pedersen O, Hansen T. (2003) Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia, 46 (2): 291-5. [PMID:12627330]

11. Ryffel GU. (2001) Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. J Mol Endocrinol, 27 (1): 11-29. [PMID:11463573]

12. Thomas H, Jaschkowitz K, Bulman M, Frayling TM, Mitchell SM, Roosen S, Lingott-Frieg A, Tack CJ, Ellard S, Ryffel GU, Hattersley AT. (2001) A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet, 10 (19): 2089-97. [PMID:11590126]

13. Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI. (1996) Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature, 384 (6608): 458-60. [PMID:8945471]