Résumés
Résumé
Le MODY (maturity onset diabetes of the young) est une forme de diabète familial, à transmission autosomique dominante et à début précoce, associé à des anomalies primaires de l’insulinosécrétion. Des mutations dans six gènes (l’enzyme glucokinase et cinq facteurs de transcription exprimés dans le pancréas) sont responsables de la plupart des cas de MODY. Cette hétérogénéité génétique est associée à une hétérogénéité métabolique et clinique faisant du MODY un modèle intéressant d’étude d’interactions génotype/phénotype dans le diabète.
Summary
Maturity onset diabetes of the young (MODY) is a subtype of familial diabetes mellitus characterised by early onset, autosomal dominant inheritance and primary defects of insulin secretion. Mutations in six known genes (the enzyme glucokinase and five transcription factors expressed in pancreatic β-cells) cause most of the MODY cases. This genetic heterogeneity is associated with metabolic and clinical heterogeneity making MODY an interesting model of genotype/phenotype interaction in diabetes.
Parties annexes
Références
- 1. Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 2001; 345: 971-80.
- 2. Timsit J, Dubois-Laforgue D, Boitard C, Bellané-Chantelot C, Velho G. Physiopathologie, présentation clinique et complications des diabètes de type MODY. In: Actualités néphrologiques. Paris: Flammarion Médecine-Sciences, 2002: 89-98.
- 3. Velho G, Froguel P, Clément K, et al. Primary pancreatic beta-cell secretory defect caused by mutations in the glucokinase in kindreds of maturity onset diabetes of the young. Lancet 1992; 340: 444-8.
- 4. Byrne MM, Sturis J, Clément K, et al. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. J Clin Invest 1994; 93: 1120-30.
- 5. Velho G, Petersen KF, Perseghin G, et al. Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects. J Clin Invest 1996; 98: 1755-61.
- 6. Hattersley AT, Beards F, Ballantyne E, et al. Mutations in the glucokinase gene of the fetus result in reduced birth weight. Nat Genet 1998; 19: 268-70.
- 7. Velho G, Blanché H, Vaxillaire M, et al. Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia 1997; 40: 217-24.
- 8. Pearson ER, Velho G, Clark P, et al. β-cell genes and diabetes: quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor 1-alpha and glucokinase mutations. Diabetes 2001; 50 (suppl 1): S101-7.
- 9. Velho G, Vaxillaire M, Boccio V, Charpentier G, Froguel P. Diabetes complications in NIDDM kindreds linked to the MODY-3 locus on chromosome 12q. Diabetes Care 1996; 19: 915-9.
- 10. Byrne MM, Sturis J, Menzel S, et al. Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes mellitus susceptibility gene MODY on chromosome 12. Diabetes 1996; 45: 1503-10.
- 11. Pontoglio M, Sreenan S, Roe M, et al. Defective insulin secretion in hepatocyte nuclear factor 1-α deficient mice. J Clin Invest 1998; 101: 2215-22.
- 12. Dukes ID, Sreenan S, Roe MW, et al. Defective pancreatic b-cell glycolytic signaling in Hepatocyte Nuclear Factor-1α-deficient mice. J Biol Chem 1998; 273: 24457-64.
- 13. Vaxillaire M, Abderrahmani A, Boutin P, et al. Anatomy of a homeoprotein revealed by the analysis of human MODY3 mutations. J Biol Chem 1999; 274: 35639-46.
- 14. Pontoglio M, Prié D, Cheret C, et al. HNF-1α controls renal glucose reabsorption in mouse and man. EMBO Rep 2000; 1: 359-65.
- 15. Isomaa B, Henricsson M, Lehto M, et al. Chronic diabetic complications in patients with MODY3 diabetes. Diabetologia 1998; 41: 467-73.
- 16. Stoffel M, Duncan SA. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4 alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA 1997; 94: 13209-14.
- 17. Thomas H, Jaschkowitz K, Bulman M, et al. A distant upstream promoter of the HNF-4alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 2001; 10: 2089-97.
- 18. Shih DQ, Screenan S, Munoz KN, et al. Loss of HNF-1 alpha function in mice leads to abnormal expression of genes involved in pancreatic islet development and metabolism. Diabetes 2001; 50: 2472-80.
- 19. Lindner TH, Njolstad PR, Horikawa Y, et al. A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1 beta. Hum Mol Genet 1999; 8: 2001-8.
- 20. Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type 2 diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997; 17: 138-9.