Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria

Human Mutation

Volumn 33, Issue 10, 2012, Pages 1485-1493

  Symoens, Sofie ^a   Syx, Delfien ^a   Malfait, Fransiska ^a   Callewaert, Bert ^a   De Backer, Julie ^a   Vanakker, Olivier ^a   Coucke, Paul ^a   De Paepe, Anne ^a  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

Author keywords

Classic Ehlers Danlos Syndrome; COL5A1; COL5A2; EDS; Type V collagen

Indexed keywords

ARTICLE; COLLAGEN DEFECT; COLLAGEN TYPE 5 ALPHA1 GENE; COLLAGEN TYPE 5 ALPHA2 GENE; DENATURING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; DISEASE CLASSIFICATION; DNA DETERMINATION; EHLERS DANLOS SYNDROME; GEL ELECTROPHORESIS; GENE; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN TISSUE; JOINT HYPERMOBILITY; MAJOR CLINICAL STUDY; NUCLEOTIDE SEQUENCE; NULL ALLELE; PRIORITY JOURNAL; SCAR FORMATION; SINGLE STRAND CONFORMATION POLYMORPHISM;

COLLAGEN TYPE V; DNA MUTATIONAL ANALYSIS; EHLERS-DANLOS SYNDROME; HUMANS; MUTATION; SKIN;

EID: 84866269985     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22137     Document Type: Article

References (40)

1. Bateman JF, Freddi S, Lamande SR, Byers P, Nasioulas S, Douglas J, Otway R, Kohonen-Corish M, Edkins E, Forrest S. 1999. Reliable and sensitive detection of premature termination mutations using a protein truncation test designed to overcome problems of nonsense-mediated mRNA instability. Hum Mutat 13:311-317.
2. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. 1998. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet 77:31-37.
3. Birk DE. 2001. Type V collagen: heterotypic type I/V collagen interactions in the regulation of fibril assembly. Micron 32:223-237.
4. Boot-Handford RP, Briggs MD. 2010. The unfolded protein response and its relevance to connective tissue diseases. Cell Tissue Res 339:197-211.
5. Bouma P, Cabral WA, Cole WG, Marini JC. 2001. COL5A1 exon 14 splice acceptor mutation causes a functional null allele, haploinsufficiency of alpha 1(V) and abnormal heterotypic interstitial fibrils in Ehlers-Danlos syndrome II. J Biol Chem 276:13356-13364.
6. Burrows NP, Nicholls AC, Richards AJ, Luccarini C, Harrison JB, Yates JR, Pope FM. 1998. 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 63:390-398.
7. Cappa F, Caridi G, Gimelli G, Ghiggeri GM. 1995. A new biallelic DNA polymorphism of the human COL5A1 gene. Hum Genet 95:599-600.
8. Chessler SD, Byers PH. 1993. BiP binds type I procollagen pro alpha chains with mutations in the carboxyl-terminal propeptide synthesized by cells from patients with osteogenesis imperfecta. J Biol Chem 268:18226-18233.
9. Czika W, Berry JJ. 2002. Using all alleles in the multiallelic versions of the SDT and combined SDT/TDT. Am J Hum Genet 71:1235-6.
10. Dalgleish R. 1997. The human type I collagen mutation database. Nucleic Acids Res 25:181-187.
11. Dalgleish R. 1998. The Human Collagen Mutation Database 1998. Nucleic Acids Res 26:253-255.
12. de Leeuw K, Goorhuis JF, Tielliu IF, Symoens S, Malfait F, de Paepe A, van Tintelen JP, Hulscher JB. 2012. Superior mesenteric artery aneurysm in a 9-year-old boy with classical Ehlers-Danlos syndrome. Am J Med Genet A 158A:626-629.
13. De Paepe A, Nuytinck L, Hausser I, Anton-Lamprecht I, Naeyaert JM. 1997. Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II. Am J Hum Genet 60:547-554.
14. Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C. 2009. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 37:e67.
15. Ganguly A, Rock MJ, Prockop DJ. 1993. Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes. Proc Natl Acad Sci USA 90:10325-10329.
16. Giunta C, Nuytinck L, Raghunath M, Hausser I, De Paepe A, Steinmann B. 2002. Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos syndrome. Am J Med Genet 109:284-290.
17. Greenspan DS, Pasquinelli AE. 1994. BstUI and DpnII RFLPs at the COL5A1 gene. Hum Mol Genet 3:385.
18. Hausser I, Anton-Lamprecht I. 1994. Differential ultrastructural aberrations of collagen fibrils in Ehlers-Danlos syndrome types I-IV as a means of diagnostics and classification. Hum Genet 93:394-407.
19. Kirschner J, Hausser I, Zou Y, Schreiber G, Christen HJ, Brown SC, Anton-Lamprecht I, Muntoni F, Hanefeld F, Bonnemann CG. 2005. Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes. Am J Med Genet A 132:296-301.
20. Malfait F, Coucke P, Symoens S, Loeys B, Nuytinck L, De Paepe A. 2005. The molecular basis of classic Ehlers-Danlos syndrome: a comprehensive study of biochemical and molecular findings in 48 unrelated patients. Hum Mutat 25:28-37.
21. Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Korkko J, Prockop DJ, De Paepe A, Coucke P, Symoens S et al. 2007. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat 28:209-221.
22. Mitchell AL, Schwarze U, Jennings JF, Byers PH. 2009. Molecular mechanisms of classical Ehlers-Danlos syndrome (EDS). Hum Mutat 30:995-1002.
23. Nicholls AC, Oliver JE, McCarron S, Harrison JB, Greenspan DS, Pope FM. 1996. An exon skipping mutation of a type V collagen gene (COL5A1) in Ehlers-Danlos syndrome. J Med Genet 33:940-946.
24. Nuytinck L, Dalgleish R, Spotila L, Renard JP, Van Regemorter N, De Paepe A. 1996. Substitution of glycine-661 by serine in the alpha1(I) and alpha2(I) chains of type I collagen results in different clinical and biochemical phenotypes. Hum Genet 97:324-329.
25. Nuytinck L, Freund M, Lagae L, Pierard GE, Hermanns-Le T, De Paepe A. 2000. Classical Ehlers-Danlos syndrome caused by a mutation in type I collagen. Am J Hum Genet 66:1398-402.
26. Orita M, Iwahana H, Kanazawa H, Hayashi K, Sekiya T. 1989. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86:2766-2770.
27. Reese MG, Eeckman FH, Kulp D, Haussler D. 1997. Improved splice site detection in Genie. J Comput Biol 4:311-323.
28. Richards AJ, Martin S, Nicholls AC, Harrison JB, Pope FM, Burrows NP. 1998. A single base mutation in COL5A2 causes Ehlers-Danlos syndrome type II. J Med Genet 35:846-848.
29. Schalkwijk J, Zweers MC, Steijlen PM, Dean WB, Taylor G, van Vlijmen IM, van Haren B, Miller WL, Bristow J. 2001. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med 345:1167-1175.
30. Schwarze U, Atkinson M, Hoffman GG, Greenspan DS, Byers PH. 2000. 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 66:1757-1765.
31. Steinmann B, Royce P, Superti-Furga A. 2002a. The Ehlers-Danlos Syndrome. In: Royce P, Steinmann B, editors. Connective tissue and its heritable disorders. New York: Wiley-Liss. 431-523.
32. Steinmann B, Royce P, Superti-Furga A. 2002b. Chondrodysplasias: general concepts and diagnostic and management considerations. In: Royce P, Steinmann B, editor. Connective tissue and its heritable disorders. New York: Wiley-Liss, Inc. p 901-908.
33. Symoens S, Malfait F, Renard M, Andre J, Hausser I, Loeys B, Coucke P, De Paepe A. 2009. COL5A1 signal peptide mutations interfere with protein secretion and cause classic Ehlers-Danlos syndrome. Hum Mutat 30:E395-E403.
34. Symoens S, Malfait F, Vlummens P, Hermanns-Le T, Syx D, De Paepe A. 2011. A Novel Splice Variant in the N-propeptide of COL5A1 Causes an EDS Phenotype with Severe Kyphoscoliosis and Eye Involvement. PLoS One 6:e20121.
35. Symoens S, Renard M, Bonod Bidaud C, Syx D, Vaganay E, Malfait F, Ricard-Blum S, Kessler E, Van Laer L, Coucke P, Ruggiero F, De Paepe A. 2011. Identification of binding partners interacting with the alpha1-N-propeptide of type V collagen. Biochem J 433:371-381.
36. Takahara K, Schwarze U, Imamura Y, Hoffman GG, Toriello H, Smith LT, Byers PH, Greenspan DS. 2002. Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I. Am J Hum Genet 71:451-465.
37. Toriello HV, Glover TW, Takahara K, Byers PH, Miller DE, Higgins JV, Greenspan DS. 1996. A translocation interrupts the COL5A1 gene in a patient with Ehlers-Danlos syndrome and hypomelanosis of Ito. Nat Genet 13:361-35.
38. Wenstrup RJ, Florer JB, Willing MC, Giunta C, Steinmann B, Young F, Susic M, Cole WG. 2000. COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS. Am J Hum Genet 66:1766-76.
39. Wenstrup RJ, Langland GT, Willing MC, D'Souza VN, Cole WG. 1996. A splice-junction mutation in the region of COL5A1 that codes for the carboxyl propeptide of pro alpha 1(V) chains results in the gravis form of the Ehlers-Danlos syndrome (type I). Hum Mol Genet 5:1733-1736.
40. Zoppi N, Gardella R, De Paepe A, Barlati S, Colombi M. 2004. Human fibroblasts with mutations in COL5A1 and COL3A1 genes do not organize collagens and fibronectin in the extracellular matrix, down-regulate alpha2beta1 integrin, and recruit alphavbeta3 Instead of alpha5beta1 integrin. J Biol Chem 279:18157-18168.