The Ehlers-Danlos Syndrome: A Heritable Collagen Disorder as Cause of Bleeding

Anne de Paepe

doi:10.1055/s-0038-1650281

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(03): 379-386
DOI: 10.1055/s-0038-1650281

Original Article

Schattauer GmbH Stuttgart

The Ehlers-Danlos Syndrome: A Heritable Collagen Disorder as Cause of Bleeding

Anne de Paepe

The Centre for Medical Genetics, University Hospital Gent, Gent, Belgium

› Author Affiliations

Abstract

PDF Download

PDF (480 kb)

References

References
1 Beighton P, De Paepe A, Danks D, Finidori G, Gedde-Dahl T, Goodman R, Hall JG, Hollister DW, Horton W, McKusick VA, Opitz JM, Pope FM, Pyeritz RE, Rimoin DL, Sillence D, Spranger JW, Thompson E, Tsipouras P, Viljoen D, Winship I, Young I. International Nosology of Heritable Disorders of Connective Tissue, Berlin, 1986. Am J Med Genet 1988; 29: 581-594
2 Beighton P, De Paepe A, Hall JG, Hollister DW, Pope FM, Pyeritz RE, Tsipouras P. Molecular nosology of heritable disorders of connective tissue. Am J Med Genet 1992; 42: 431-448
3 Byers PH. Disorders of collagen biosynthesis and structure. In: The Metabolic Basis of Inherited Disease Scriver CHR, Beaudet AL, Sly WS, Valle D. eds McGraw Hill; 1989: 2805-2842
4 Beighton P. The Ehlers-Danlos syndromes. In: McKusick’s Heritable disorders of connective tissue Fifth Edition Beighton P. ed University of Cape Town Medical School; Cape Town, South Africa: 1993: 189-251
5 Steinmann B, Royce PM, Superti-Furga A. The Ehlers-Danlos Syndrome. In: Connective Tissue and its Heritable Disorders. Molecular, genetic and medical aspects Royce PM, Steinmann B. eds Wiley-Liss Inc; 1993: 351-407
6 Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of Heritable Connective Tissue Disorders. A review. Stroke 1994; 25 (04) 889-903
7 Kielty CM, Hopkinson I, Grant ME. Collagen: The collagen family: structure, assembly and organization in the extracellular matrix. In: Connective Tissue and its Heritable Disorders. Molecular, genetic and medical aspects Royce PM, Steinmann B. eds Wiley-Liss Inc; 1993: 103-147
8 Burgeson RE. New collagens. New concepts. Ann Rev Cell Biol 1988; 4: 551-577
9 Cole WG. Collagen genes: Mutations affecting collagen structure and expression. Progress Nuc Acids Res and Mol Biol 1994; 47: 29-80
10 Van Der Rest M, Garrone R. Collagen family of proteins. Faseb J 1991; 5: 2814-2823
11 Chu M-L, Prockop D. Collagen: Gene structure. In: Connective Tissue and its Heritable Disorders. Molecular, genetic and medical aspects Royce PM, Steinmann B. eds Wiley-Liss Inc; 1993: 149-165
12 Fleischmajer R, Olsen BR, Kuhn K. Biology, chemistry and pathology of collagen. Ann NY Acad Sci 1985; 460: 1-224
13 Tilstra DJ, Byers PH. Molecular Basis of Hereditary Disorders of Connective Tissue. Annu Rev Med 1994; 45: 149-163
14 Kuivaniemi H, Tromp G, Prockop DJ. Mutations in collagen genes: causes of rare and common diseases in humans. Faseb J 1991; 5: 2052-2059
15 Slack JL, Liska DJ, Bomstein P. Regulation of expression of the type I collagen genes. Am J Med Genet 1993; 45: 140-151
16 Ruteshouser EC, de Crombrugghe B. Purification of BBF, a DNA-binding protein recognizing a positive cis-acting element in the mouse a,(III) collagen promoter. J Biol Chem 1992; 267 (20) 14398-14404
17 Beighton P, Curtis D. X-linked Ehlers-Danlos syndrome type V; the next generation. Clin Genet 1985; 27: 472-478
18 Byers PH, Siegel RC, Holbrook KA, Narayanan AS, Bomstein P, Hall JG. X-linked cutis laxa. Defective cross-link formation in collagen due to decreased lysyl oxidase activity. New Engl J Med 1980; 303: 61-65
19 Pope FM, Narcisi P, Nicholls AC, Liberman M, Oorthuys JWE. Clinical presentation of Ehlers-Danlos syndrome type IV. Arch Dis Child 1988; 63: 1016-1025
20 Anstey A, Mayne K, Winter M, Van De Pette J, Pope FM. Platelet and coagulation studies in Ehlers-Danlos syndrome. Brit J Dermatol 1991; 125: 155-163
21 Karaca M, Cronberg L, Nilsson IM. Abnormal platelet-collagen reaction in Ehlers-Danlos syndrome. Scand J Haemat 1972; 9: 465-469
22 Uden A. Collagen and bleeding diathesis in Ehlers-Danlos syndrome. Scand J Haematol 1982; 28: 425-430
23 De Paepe A. Genetic Changes in the Collagens in Osteogenesis Imperfecta and the Ehlers-Danlos syndromes. . Thesis submitted as partial fulfilment of the requirements for the degree of “Geaggregeerde voor het Hoger Onderwijs” 1992
24 Pope FM, Nicholls AC, Narcisi P, Temple A, Chia Y, Fryer P, De Paepe A, De Groote WR, McEwan JR, Compston DA, Oorthuys H, Davies J, Dinwoodie DL. Type III collagen mutations in Ehlers-Danlos syndrome type IV and other related disorders. Clin Exp Dermatol 1988; 13: 285-302
25 De Paepe A, Thaler B, Van Gijsegem M, Van Hoecke D, Matton M. Obstetrical problems in patients with Ehlers-Danlos syndrome type IV. J Obstet Gynecol Biol 1989; 33: 189-193
26 Tromp G, Kuivaniemi H, Stolle C, Pope FM, Prockop DJ. Single base mutation in the type III procollagen gene that converts the codon for glycine 883 to aspartate in a mild variant of Ehlers-Danlos syndrome IV. J Biol Chem 1989; 264 (32) 19313-19317
27 Richards AJ, Lloyd JC, Ward PN, De Paepe A, Narcisi P, Pope FM. Characterisation of a glycine to valine substitution of aminoacid position 910 of the triple-helical region of type III collagen in a patient with Ehlers-Danlos syndrome type IV. J Med Genet 1991; 28: 458-463
28 Kontusaari S, Tromp G, Kuivaniemi H, Romanic AM, Prockop DJ. A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms. J Clin Invest 1990; 86: 1465-1473
29 Wenstrup RJ, Murad S, Pinnell SR. Ehlers-Danlos syndrome type VI: Clinical manifestations of collagen lysyl hydroxylase deficiency. J Pediatr 1989; 115: 405-409
30 Royce PM, Steinmann B, Vogel A, Steinhorst U, Kohlschuetter A. Brittle cornea syndrome : A heritable connective tissue disorder distinct from Ehlers-Danlos syndrome type VI and fragilitas oculi, with spontaneous perforations of the eye, blue sclerae, red hair, and normal collagen lysyl hydroxylation. Eur J Pediatr 1990; 149: 465-469
31 Cole WG, Evans R, Sillence DO. The clinical features of Ehlers-Danlos syndrome type VII due to a deletion of 24 amino acids from the pro-al(I) chain of type I procollagen. J Med Genet 1987; 24: 698-701
32 Nusgens BV, Verellen-Dumoulin Ch, Hermanns-Le D, De Paepe A, Nuytinck L, Pierard GE, Lapiere CHM. Evidence for a relationship between Ehlers-Danlos type VII(C) in humans and bovine dermatosparaxis. Nature Genet 1992; 1: 214-217
33 Wertelecki W, Smith LT, Byers P. Initial observations of human dermatosparaxis: Ehlers-Danlos syndrome type VIIC. J Ped 1992; 121 (04) 558-564
34 Smith LT, Wertelecki W, Milstone LM, Petty EM, Seashore MR, Braverman IM, Jenkins TG, Byers PH. Human dermatosparaxis: A form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen. Am J Hum Genet 1992; 51: 235-244
35 Reardon W, Winter RM, Smith LT, Lake BD, Rossiter M, Baraitser M. The natural history of human dermatosparaxis (Ehlers-Danlos syndrome type VIIC). Clin Dysmorph 1995; 4: 1-11
36 Stewart RE, Hollister DW, Rimoin DL. A new variant of Ehlers-Danlos syndrome: an autosomal dominant disorder of fragile skin, abnormal scarring, and generalized periodontitis. Birth Defects: Original Article Series 1977; XIII, 3B 85-93
37 Cunniff C, Williamson-Kruse L. Ehlers-Danlos syndrome, type VIII presenting with periodontitis and prolonged bleeding time. Clin Dysmorph 1995; 4: 145-149
38 Ameson MA, Hammerschmidt DE, Furcht LT, King RA. A new form of Ehlers-Danlos syndrome. Fibronectin corrects defective platelet function. J Am Med Assoc 1980; 244: 144-147
39 Pope FM, Martin GR, Lichtenstein JR, Penttinen R, Gerson B, Rowe DW, McKusick VA. Patients with Ehlers-Danlos syndrome type IV lack type III collagen. Proc Nat Acad Sci 1975; 72: 1314-1316
40 Pinnell SR, Krane SM, Kenzora JE, Glimcher MJ. A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease. N Engl J Med 1972; 286: 1013-1020
41 Nicholls AC, McCarron S, Narcisi P, Pope FM. Molecular abnormalities of type V collagen in Ehlers-Danlos syndrome. Am J Hum Genet 1994; 55 (03) A1358
42 Hausser I, Anton-Lamprecht I. Differential ultrastructural aberrations of collagen fibrils in Ehlers-Danlos syndrome types I-IV as a means of diagnostics and classification. Hum Genet 1994; 3: 394-407
43 Hautala T, Byers MG, Eddy RL, Shows TB, Kivirikko KI, Myllya R. Cloning of human lysyl hydroxylase. Complete cDNA-derived amino acid sequence and assignment of the gene (PLOD) to chromosome Ip36.2→p36.3. Genomics 1992; 13: 62-69
44 Nerlich AG, Stoss H, Lehmann H, Krieg T, Muller PK. Pathomorphologi-cal and biochemical alterations in Ehlers-Danlos syndrome type IV. Path Res Pract 1994; 190: 697-706
45 Tromp G, Kuivaniemi H, Shikata H, Prockop D. A single base mutation that substitutes serine for glycine 790 of the α(III) chain of type IV procollagen exposes an Arg and causes EDS IV. J Biol Chem 1989; 264 03: 1349-1352
46 Richards AJ, Ward PN, Narcisi P, Nicholls AC, Lloyd JC, Pope FM. A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An unaffected family member is mosaic for the mutation. Hum Genet 1992; 89: 414-418
47 Kontusaari S, Tromp G, Kuivaniemi H, Stolle C, Pope M, Prockop DJ. Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leucocytes of the asymptomatic and mosaic mother. Am J Hum Genet 1992; 51: 497-507
48 Johnson PH, Richards AJ, Pope FM, Hopkinson DA. A COL3A1 glycine to glutamic acid substitution in a patient with Ehlers-Danlos syndrome type IV detected by denaturing gradient gel electrophoresis. J Inher Metab Dis 1992; 15: 426-430
49 Richards AJ, Narcisi P, Lloyd JC, Johnson PH, Hopkinson DA, Pope FM. Substitution of glycines 1000,1003 and 1006 in type III collagen all cause the acrogeric form of EDS IV, and destabilise the collagen triple helix. Matrix 1993; 13: 47
50 Early J, Tromp G, Kuivaniemi H, Gatalica Z, Prockop DJ. A mutation that substitutes Arg for Gly 136 in collagen III identified in a patient with fibro-muscular dysplasia and aortic aneurysm. Matrix 1993; 13: 34
51 Narcisi P, Wu Y, Tromp G, Earley JJ, Richards AJ, Pope FM, Kuivaniemi H. Single base mutation that substitutes glutamic acid for glycine 1021 in the COL3A1 gene and causes Ehlers-Danlos syndrome type IV. Am J Med Genet 1993; 46: 278-283
52 Richards A, Narcisi P, Lloyd J, Ferguson C, Pope M. The substitution of glycine 661 by arginine in type III collagen produces mutant molecules with different thermal stabilities and causes Ehlers-Danlos syndrome type IV. J Med Genet 1993; 30: 690-693
53 Nuytinck L, De Paepe A, Renard JP, Adriaens F, Leroy J. Single-strand conformation polymorphism (SSCP) analysis of the COL3A1 gene detects a mutation that results in the substitution of glycine 1009 to valine and causes severe Ehlers-Danlos syndrome type IV. Hum Mut 1994; (03) 3: 268-274
54 Narcisi P, Richards AJ, Ferguson SD, Pope FM. A family with Ehlers-Danlos syndrome type Ill/articular hypermobility syndrome has a glycine 637 to serine substitution in type IV collagen. Hum Mol Genet 1994; 3: 1617-1620
55 Madhatheri SL, Tromp G, Gustavson KH, Kuivaniemi H. Substitution of glutamic acid for glycine 589 in the triple-helical domain of type III procollagen (COL3A1) in a family with variable phenotype of the Ehlers-Danlos syndrome type IV. Hum Mol Genet 1994; (03) 3: 511-512
56 McGrory J, Costa T, Cole WG. Acrogeric Ehlers-Danlos type IV due to a novel heterozygous G499D substitution in the al(III) chain of type III collagen. Matrix Biol 1994; 14 (05) 393
57 Goldstein JA, Schwarze U, Witz A, Byers PH. Marked heterogeneity in COL3A1 mutations that produce the EDS type IV phenotype. Matrix Biol 1994; 14 (05) 392-393
58 Tromp G, De Paepe A, Nuytinck L, Madhatheri S, Kuivaniemi H. Substitution of valine for glycine 793 in type III procollagen in Ehlers-Danlos syndrome type IV. Hum Mut 1995; 5: 179-181
59 Kuivaniemi H, Kontusaari S, Tromp G, Zhao M, Sabol C, Prockop DJ. Identical G+l to A mutations in three different introns of the type III procollagen gene (COL3A1) produce different patterns of RNA splicing in three variants of Ehlers-Danlos syndrome IV. J Biol Chem 1990; 265 (20) 12067-12074
60 Thakker-Varia S, Anderson D, Kuivaniemi H, Tromp G, Prockop DJ, Stolle C. An exon deletion in type III procollagen mRNA is associated with intracellular degradation of the abnormal protein in a patient with EDS IV. Matrix 1990; 10: 249-250
61 Cole WG, Chiodo AA, Lamande SR, Janeczko R, Ramirez F, Dahl H-H, Chan D, Bateman JF. A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. J Biol Chem 1990; 265: 17070-17077
62 Lee B, D’Alessio M, Vissing H, Ramirez F, Steinmann B, Superti-Furga A. Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV. Am J Hum Genet 1991; 48: 511-517
63 Wu Y, Kuivaniemi H, Tromp G, Strobel D, Romanic AM, Prockop DJ. Temperature sensitivity of aberrant RNA splicing with a mutation in the G+5 position of intron 37 of the gene for type III procollagen from a patient with Ehlers-Danlos syndrome type IV. Hum Mut 1993; 2: 28-36
64 Anderson DW, Thakker-Varia S, Stolle CA. A ^G+1 → A change in IVS20 of the type IV procollagen gene leads to cryptic splicing of the mRNA in an EDS IV patient. Matrix 1991; 13: 34
65 Lloyd J, Narcisi P, Richards A, Pope FM. A T+6 to C+6 mutation in the donor splice site of COL3A1 IVS7 causes exon skipping and results in Ehlers-Danlos syndrome type IV. J Med Genet 1993; 30: 376-380
66 Richards AJ, Narcisi P, Ferguson C, Cobben JM, Pope FM. Two new mutations affecting the donor splice site of COL3A1 IVS37 and causing skipping of exon 37 in patients with Ehlers-Danlos syndrome type IV. Hum Mol Genet 1994; 3: 1901-1902
67 McGookey DJ, Smith ACM, Waldstein G, Byers PH. Mosaicism for a deletion in one of the type III collagen alleles indicates that the deletion occurred after identification of cells for recruitment to different cell lineages early in human development. Am J Hum Genet 1989; 45: A206
68 Milewicz McGookey D, Witz AM, Smith ACM, Manchester DK, Waldstein G, Byers PH. Parental somatic and germ-line mosaicism for a multi-exon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring. Am J Hum Genet 1993; 53: 62-70
69 Vissing H, D’Alessio M, Lee B, Ramirez F, Byers PH, Steinmann B, Superti-Furga A. Multi-exon deletion in the procollagen III gene is associated with mild Ehlers-Danlos syndrome type IV. J Biol Chem 1991; 266 (06) 5244-5248
70 Lee B, Vitale E, Superti-Furga A, Steinmann B, Ramirez F. G to T transversion at position +5 of a splice donor site causes skipping of the preceding exon in the type III procollagen transcripts of a patient with Ehlers-Danlos syndrome type IV. J Biol Chem 1991; 266 (08) 5256-5259
71 Richards AJ, Lloyd JC, Narcisi P, Ward PN, Nicholls AC, De Paepe A, Pope FM. A 27-bp deletion from one allele of the type III collagen gene (COL3A1) in a large family with Ehlers-Danlos syndrome type IV. Hum Genet 1992; 88: 325-330
72 Loughlin J, Irven C, Hardwick LJ, Butcher S, Walsh S, Wordsworth P, Sykes B. Linkage of the gene that encodes the al chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II). Hum Mol Genet 1995; 4: 1649-1651
73 Cikrit DF, Miles JH, Silver D. Spontaneous arterial perforation: The Ehlers-Danlos specter. J Vase Surg 1987; 5: 248-255
74 Dolan P, Sisko F, Riley E. Anesthetic considerations for Ehlers-Danlos syndrome. Anesthesiology 1980; 52: 266-269
75 De Paepe A. Ehlers-Danlos syndrome type IV: clinical and molecular aspects and guidelines for diagnosis and management. Dermatology 1994; 189 suppl (Suppl. 02) 21-25