Résumés
Résumé
Le syndrome d’Ehlers-Danlos constitue un groupe hétérogène de maladies génétiques du tissu conjonctif. Il est caractérisé par une peau hyper-extensible, des articulations anormalement mobiles et des vaisseaux fragiles. Les anomalies moléculaires responsables de cette maladie portent souvent sur les collagènes et les enzymes assurant leur maturation. La forme classique du syndrome, qui sera principalement discutée dans cet article, est majoritairement due à des mutations du collagène V, un collagène fibrillaire présent en petite quantité dans les tissus affectés. Cependant, des anomalies moléculaires du collagène I ou de la ténascine peuvent aussi être responsables de ce syndrome. De plus, chez la souris, l’invalidation de gènes codant pour d’autres molécules matricielles (SPARC, thrombospondine, petits protéoglycanes riches en leucine) conduit à des phénotypes mimant ce syndrome et suggère que ces molécules pourraient donc être impliquées. Comme les anomalies du collagène V restent à ce jour principalement responsables de cette affection, nous discuterons son rôle physiologique à la lumière des observations cliniques et fondamentales. Nous tenterons de comprendre comment le collagène V interagit avec les autres molécules pour déterminer les caractéristiques tissulaires.
Summary
Ehlers-Danlos syndrome (EDS) is a heterogeneous heritable connective tissue disorder characterized by hyperextensible skin, hypermobile joints and fragile vessels. The molecular causes of this disorder are often, although not strictly, related to collagens and to the enzymes that process these proteins. The classical form of the syndrome, which will be principally discussed in this review, can be due to mutations on collagen V, a fibrillar collagen present in small amounts in affected tissues. However, collagen I and tenascin have also been demonstrated to be involved in the same type of EDS. Moreover gene disruption of several other matrix molecules (thrombospondin, SPARC, small leucine rich proteoglycans...) in mice, lead to phenotypes that mimic EDS and these molecules have thus emerged as new players. As collagen V remains the prime candidate, we discuss, based on fundamental and clinical observations, its physiological role. We also explore its potential interactions with other matrix molecules to determine tissue properties.
Parties annexes
Références
- 1. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Am J Med Genet 1998; 77: 31-7.
- 2. Steinmann B, Royce PM, Supeti-Furga A. the Elhers-danlos syndrome. In: Royce PM, Steinman B, eds. Connective tissue and its heritable disorders. New York: Wiley-Liss, 1993 : 351-408.
- 3. Mao JR, Bristow J. The Ehlers-Danlos syndrome: on beyond collagens. J Clin Invest 2001; 107: 1063-9.
- 4. Fichard A, Kleman JP, Ruggiero F. Another look at collagen V and XI molecules. Matrix Biol 1995; 14: 515-31.
- 5. Birk DE. Type V collagen: heterotypic type I/V collagen interactions in the regulation of fibril assembly. Micron 2001; 32: 223-37.
- 6. Erickson HP. Tenascin-C, tenascin-R and tenascin-X: a family of talented proteins in search of functions. Curr Opin Cell Biol 1993; 5: 869-76.
- 7. Nicholls AC, McCarron SM, Narcisi P, Pope FM. Molecular abnormalities of type V collagen in the Ehlers-Danlos syndrome. Am J Hum Genet 1994; 62: 523-8.
- 8. Michalickova K, Susic M, Willing MC, Wenstrup RJ, Cole WG. Mutations of the α 2(V) chain of type V collagen impair matrix assembly and produce Ehlers-Danlos syndrome type I. Hum Mol Genet 1998; 7: 249-55.
- 9. Richards AJ, Martin S, Nicholls AC, Harrison JB, Pope FM, Burrows NP. A single base mutation in COL5A2 causes Ehlers-Danlos syndrome type II. J Med Genet 1998; 35: 846-8.
- 10. Toriello HV, Glover TV, Takahara K, et al. A translocation interrupts the COL5A1 gene in a patient with Ehlers-Danlos syndrome and hypomelanosis of Ito. Nat Genet 1996; 13: 361-5
- 11. Wenstrup RJ, Langland GT, Willing MC, D’Souza VN, Cole WG. A splice junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro-α1(V) chains results in gravis form of Ehlers-Danlos syndrome (type I). Hum Mol Genet 1996; 5: 1733-6.
- 12. Nicholls AC, Oliver JE, McCarron S, Harrison JB, Greenspan DS, Pope FM. An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome. J Med Genet 1996; 33: 940-6.
- 13. De Paepe A, Nuytinck L, Hausser I, Anton-Lamprecht I, Naeyaert JM. Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II. Am J Hum Genet 1997; 60: 547-54
- 14. Burrows NP, Nicholls AC, Richards AJ, et al. A point mutation in an intronic branch site results in aberrant splicing of COL5A1 and in Ehlers-Danlos syndrome type II in two British families. Am J Hum Genet 1998; 63: 390-8.
- 15. Giunta C, Steinmann B. Characterization of 11 new mutations in COL5A1 of individuals with Ehlers-Danlos syndrome type IV: preliminary comparison of RNase cleavage, EMC and DHPLC assays. Hum Mutat 2000; 16: 176-7.
- 16. Schwarze U, Atkinson M, Hoffman GG, Greenspan DS, Byers PH. Null alleles of the COL5A1 gene of type V collagen are a cause of the classical forms of Ehlers-Danlos syndrome (types I and II). Am J Hum Genet 2000; 66: 1757-65.
- 17. Bouma P, Cabral WA, Cole WG, Marini JC. COL5A1 exon 14 splice acceptor mutation causes a functional null allele, haploinsufficiency of α1(V) and abnormal heterotypic interstitial fibrils in Ehlers-Danlos syndrome II. J Biol Chem 2001; 276: 13356-64.
- 18. Imamura Y, Scott IC, Greenspan DS. The pro-α3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains. J Biol Chem 2000; 275: 8749-59.
- 19. Chernousov MA, Rothblum K, Tyler WA, Stahl RC, Carey DJ. Schwann cells synthesize type V collagen that contains a novel α4 chain. Molecular cloning, biochemical characterization, and high affinity heparin binding of α4(V) collagen. J Biol Chem 2000; 275: 28208-15.
- 20. Nuytinck L, Freund M, Lagae L, Pierard GE, Hermanns-Le T, De Paepe A. Classical Ehlers-Danlos syndrome caused by a mutation in type I collagen. Am J Hum Genet 2000; 66: 1398-402.
- 21. Burch GH, Gong Y, Liu W, et al. Tenascin-X deficiency is associated with Ehlers-Danlos syndrome. Nat Genet 1997; 17: 104-8.
- 22. Schalkwijk J, Zweers MC, Steijlen PM, et al. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med 2001; 345: 1167-75.
- 23. Lohler J, Timpl R, Jaenisch R. Embryonic lethal mutation in mouse collagen I gene causes rupture of blood vessels and is associated with erythropoietic and mesenchymal cell death. Cell 1984; 38: 597-607.
- 24. Chipman SD, Sweet HO, Davisson MT, et al. Defective proa2(I) collagen synthesis in a recessive mutation in mice: a model of human osteogenesis imperfecta. Proc Natl Acad Sci USA 1993; 90: 1705-5.
- 25. Liu X, Wu H, Byrne M, Krane S, Jaenisch R. Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc Natl Acad Sci USA 1997; 94: 1852-6.
- 26. Andrikopoulos K, Liu X, Keene DR, Jaenisch R, Ramirez F. Targeted mutation in the col5a2 gene reveals a regulatory role for type V collagen during matrix assembly. Nat Genet 1995; 9 :31-6.
- 27. Mao JR, Taylor G, Dean WB, et al. Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition. Nat Genet 2002; 30: 421-5.
- 28. Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H. Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol 1998; 141: 1277-86.
- 29. Svensson L, Aszodi A., Reinholt FP, Fassler R, Heinegard D, Oldberg A. Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon J Biol Chem 1999; 274: 9636-47.
- 30. Danielson KG, Baribault H, Holmes DF, Graham H, Kadler KE, Iozzo RV. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J Cell Biol 1997; 136: 729-43.
- 31. Fushimi H, Kameyama M, Shinkai H. Deficiency of the core proteins of dermatan sulphate proteoglycans in a variant form of Ehlers-Danlos syndrome. J Intern Med 1989; 226: 409-16
- 32. Quentin E, Gladen A, Roden L, Kresse H. A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. Proc Natl Acad Sci USA 1990; 87: 1342-6.
- 33. Kyriakides TR, Zhu YH, Smith LT, et al. Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. J Cell Biol 1998 ; 140: 419-30.
- 34. Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. J Clin Invest 2001; 107: 1049-54.
- 35. Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE. Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons. J Cell Biol 2000; 151: 779-88.
- 36. Fichard A, Tillet E, Delacoux F, Garrone R, Ruggiero F. Human recombinant α1(V) collagen chain. Homotrimeric assembly and subsequent processing. J Biol Chem 1997; 272: 30083-7.
- 37. Delacoux F, Fichard A, Geourjon C, Garrone R, Ruggiero F. Molecular features of the collagen V heparin binding site. J Biol Chem 1998; 273: 15069-76.
- 38. Chanut-Delalande H, Fichard A, Bernocco S, Garrone R, Hulmes DJ, Ruggiero F. Control of heterotypic fibril formation by collagen V is determined by chain stoichiometry. J Biol Chem 2001; 276: 24352-9.
- 39. Scott JE, Thomlinson AM. The structure of interfibrillar proteoglycan bridges (shape modules) in extracellular matrix of fibrous connective tissues and their stability in various chemical environments. J Anat 1998; 192: 391-405.
- 40. Mundlos S, Chan D, McGill J, Bateman JF. An α1(II) Gly913 to Cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis. Am J Med Genet 1996; 63: 129-36.
- 41. Ruggiero F, Comte J, Cabanas C, Garrone R. Structural requirements for α1β1 and α2β1 integrin mediated cell adhesion to collagen V. J Cell Sci 1996; 109: 1865-74.
- 42. Tillet E, Ruggiero F, Nishiyama A, Stallcup WB. The membrane-spanning proteoglycan NG2 binds to collagens V and VI through the central nonglobular domain of its core protein. J Biol Chem 1997; 272: 10769-76.
- 43. Vogel W, Brakebusch C, Fassler R, Alves F, Ruggiero F, Pawson T. Discoidin domain receptor 1 is activated independently of β(1) integrin. J Biol Chem 2000; 275: 5779-84.
- 44. De Paepe A. The Ehlers-Danlos syndrome: a heritable collagen disorder as cause of bleeding. Thromb Haemost 1996; 75: 379-86.