Skip to main content
SpringerLink
Log in

COL7A1 and Its Role in Dystrophic Epidermolysis Bullosa

  • Chapter
  • First Online:
Blistering Diseases

  • 1356 Accesses

Abstract

Type VII collagen is the major component of the anchoring fibrils (AF) that anchor the basal lamina to the dermal collagen fibrils. It is encoded by the collagen VII gene (COL7A1). Dystrophic epidermolysis bullosa (DEB) is an inherited skin fragility disorder, and blistering occurs in the sub-lamina densa zone at the level of AF. DEB results from different mutations in the type VII collagen gene (COL7A1). The nature of mutations in COL7A1 and their positions correlate reasonably logically with the severity of the resulting phenotypes of dystrophic EB.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AF:

Anchoring fibrils

COL7A1:

Type VII collagen gene

DDEB:

Autosomal dominant DEB

DEB:

Dystrophic epidermolysis bullosa

RDEB:

Autosomal recessive DEB

References

  1. Ryynanen M, Knowlton RG, Parente MG, Chung LC, Chu ML, Uitto J. Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa. Am J Hum Genet. 1991;49(4):797–803.

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Hovnanian A, Duquesnoy P, Blanchet-Bardon C, Knowlton RG, Amselem S, Lathrop M, et al. Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII collagen gene. J Clin Invest. 1992;90(3):1032–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Christiano AM, Greenspan DS, Lee S, Uitto J. Cloning of human type VII collagen. Complete primary sequence of the alpha 1(VII) chain and identification of intragenic polymorphisms. J Biol Chem. 1994;269(32):20256–62.

    CAS  PubMed  Google Scholar 

  4. Christiano AM, Hoffman GG, Chung-Honet LC, Lee S, Cheng W, Uitto J, et al. Structural organization of the human type VII collagen gene (COL7A1), composed of more exons than any previously characterized gene. Genomics. 1994;21(1):169–79.

    Article  CAS  PubMed  Google Scholar 

  5. Sakai LY, Keene DR, Morris NP, Burgeson RE. Type VII collagen is a major structural component of anchoring fibrils. J Cell Biol. 1986;103(4):1577–86.

    Article  CAS  PubMed  Google Scholar 

  6. Burgeson RE. Type VII collagen, anchoring fibrils, and epidermolysis bullosa. J Invest Dermatol. 1993;101(3):252–5.

    Article  CAS  PubMed  Google Scholar 

  7. Ruoslahti E, Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science. 1987;238(4826):491–7.

    Article  CAS  PubMed  Google Scholar 

  8. Greenspan DS. The carboxyl-terminal half of type VII collagen, including the non-collagenous NC-2 domain and intron/exon organization of the corresponding region of the COL7A1 gene. Hum Mol Genet. 1993;2(3):273–8.

    Article  CAS  PubMed  Google Scholar 

  9. Lunstrum GP, Kuo HJ, Rosenbaum LM, Keene DR, Glanville RW, Sakai LY, et al. Anchoring fibrils contain the carboxyl-terminal globular domain of type VII procollagen, but lack the amino-terminal globular domain. J Biol Chem. 1987;262(28):13706–12.

    CAS  PubMed  Google Scholar 

  10. Fine JD, Bruckner-Tuderman L, Eady RA et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol. 2014;70:1103–26.

    Google Scholar 

  11. McGrath JA, Ishida-Yamamoto A, O’Grady A, Leigh IM, Eady RA. Structural variations in anchoring fibrils in dystrophic epidermolysis bullosa: correlation with type VII collagen expression. J Invest Dermatol. 1993;100(4):366–72.

    Article  CAS  PubMed  Google Scholar 

  12. McGrath JA, Schofield OM, Eady RA. Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features. Br J Dermatol. 1994;130(5):617–25.

    Article  CAS  PubMed  Google Scholar 

  13. Christiano AM, Anhalt G, Gibbons S, Bauer EA, Uitto J. Premature termination codons in the type VII collagen gene (COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa. Genomics. 1994;21(1):160–8.

    Article  CAS  PubMed  Google Scholar 

  14. Christiano AM, McGrath JA, Tan KC, Uitto J. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance. Am J Hum Genet. 1996;58(4):671–81.

    PubMed Central  CAS  PubMed  Google Scholar 

  15. Whittock NV, Ashton GH, Mohammedi R, Mellerio JE, Mathew CG, Abbs SJ, et al. Comparative mutation detection screening of the type VII collagen gene (COL7A1) using the protein truncation test, fluorescent chemical cleavage of mismatch, and conformation sensitive gel electrophoresis. J Invest Dermatol. 1999;113(4):673–86.

    Article  CAS  PubMed  Google Scholar 

  16. Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix Biol. 1999;18(1):29–42.

    Article  CAS  PubMed  Google Scholar 

  17. Posteraro P, Pascucci M, Colombi M, Barlati S, Giannetti A, Paradisi M, et al. Denaturing HPLC-based approach for detection of COL7A1 gene mutations causing dystrophic epidermolysis bullosa. Biochem Biophys Res Commun. 2005;338(3):1391–401.

    Article  CAS  PubMed  Google Scholar 

  18. Jarvikallio A, Pulkkinen L, Uitto J. Molecular basis of dystrophic epidermolysis bullosa: mutations in the type VII collagen gene (COL7A1). Hum Mutat. 1997;10(5):338–47.

    Article  CAS  PubMed  Google Scholar 

  19. Kivirikko S, Li K, Christiano AM, Uitto J. Cloning of mouse type VII collagen reveals evolutionary conservation of functional protein domains and genomic organization. J Invest Dermatol. 1996;106(6):1300–6.

    Article  CAS  PubMed  Google Scholar 

  20. Dunnill MG, McGrath JA, Richards AJ, Christiano AM, Uitto J, Pope FM, et al. Clinicopathological correlations of compound heterozygous COL7A1 mutations in recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 1996;107(2):171–7.

    Article  CAS  PubMed  Google Scholar 

  21. Bruckner-Tuderman L, Nilssen O, Zimmermann DR, Dours-Zimmermann MT, Kalinke DU, Gedde-Dahl Jr T, et al. Immunohistochemical and mutation analyses demonstrate that procollagen VII is processed to collagen VII through removal of the NC-2 domain. J Cell Biol. 1995;131(2):551–9.

    Article  CAS  PubMed  Google Scholar 

  22. Kern JS, Kohlhase J, Bruckner-Tuderman L, Has C. Expanding the COL7A1 mutation database: novel and recurrent mutations and unusual genotype-phenotype constellations in 41 patients with dystrophic epidermolysis bullosa. J Invest Dermatol. 2006;126(5):1006–12.

    Article  CAS  PubMed  Google Scholar 

  23. Sawamura D, Goto M, Yasukawa K, Sato-Matsumura K, Nakamura H, Ito K, et al. Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa. J Hum Genet. 2005;50(10):543–6.

    Article  PubMed  Google Scholar 

  24. Christiano AM, McGrath JA, Uitto J. Influence of the second COL7A1 mutation in determining the phenotypic severity of recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 1996;106(4):766–70.

    Article  CAS  PubMed  Google Scholar 

  25. Hovnanian A, Rochat A, Bodemer C, Petit E, Rivers CA, Prost C, et al. Characterization of 18 new mutations in COL7A1 in recessive dystrophic epidermolysis bullosa provides evidence for distinct molecular mechanisms underlying defective anchoring fibril formation. Am J Hum Genet. 1997;61(3):599–610.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Ryoo YW, Kim BC, Lee KS. Characterization of mutations of the type VII collagen gene (COL7A1) in recessive dystrophic epidermolysis bullosa mitis (M-RDEB) from three Korean patients. J Dermatol Sci. 2001;26(2):125–32.

    Article  CAS  PubMed  Google Scholar 

  27. Bruckner-Tuderman L. Epidermolysis bullosa. In: Royce PM, Steinmann B, editors. Connective tissue and its heritable disorders molecular, genetic and medical aspects. New York: Wiley-Liss; 1993. p. 507–32.

    Google Scholar 

  28. Christiano AM, Uitto J. Molecular complexity of the cutaneous basement membrane zone. Revelations from the paradigms of epidermolysis bullosa. Exp Dermatol. 1996;5(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  29. Fine JD, Johnson LB, Cronce D, Wright JT, Leigh IM, McCollough M, et al. Intracytoplasmic retention of type VII collagen and dominant dystrophic epidermolysis bullosa: reversal of defect following cessation of or marked improvement in disease activity. J Invest Dermatol. 1993;101(2):232–6.

    Article  CAS  PubMed  Google Scholar 

  30. Hashimoto K, Eng AM. Transient bullous dermolysis of the newborn. Retention of anchoring fibril- and basal lamina-like structures in keratinocytes and evidence of collagenolysis. J Cutan Pathol. 1992;19(6):496–501.

    Article  CAS  PubMed  Google Scholar 

  31. Sakuntabhai A, Hammami-Hauasli N, Bodemer C, Rochat A, Prost C, Barrandon Y, et al. Deletions within COL7A1 exons distant from consensus splice sites alter splicing and produce shortened polypeptides in dominant dystrophic epidermolysis bullosa. Am J Hum Genet. 1998;63(3):737–48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Cserhalmi-Friedman PB, McGrath JA, Mellerio JE, Romero R, Salas-Alanis JC, Paller AS, et al. Restoration of open reading frame resulting from skipping of an exon with an internal deletion in the COL7A1 gene. Lab Invest. 1998;78(12):1483–92.

    CAS  PubMed  Google Scholar 

  33. Christiano AM, Fine JD, Uitto J. Genetic basis of dominantly inherited transient bullous dermolysis of the newborn: a splice site mutation in the type VII collagen gene. J Invest Dermatol. 1997;109(6):811–4.

    Article  CAS  PubMed  Google Scholar 

  34. Jiang W, Bu D, Yang Y, Zhu X. A novel splice site mutation in collagen type VII gene in a Chinese family with dominant dystrophic epidermolysis bullosa pruriginosa. Acta Derm Venereol. 2002;82(3):187–91.

    Article  CAS  PubMed  Google Scholar 

  35. Hammami-Hauasli N, Schumann H, Raghunath M, Kilgus O, Luthi U, Luger T, et al. Some, but not all, glycine substitution mutations in COL7A1 result in intracellular accumulation of collagen VII, loss of anchoring fibrils, and skin blistering. J Biol Chem. 1998;273(30):19228–34.

    Article  CAS  PubMed  Google Scholar 

  36. Sato-Matsumura KC, Yasukawa K, Tomita Y, Shimizu H. Toenail dystrophy with COL7A1 glycine substitution mutations segregates as an autosomal dominant trait in 2 families with dystrophic epidermolysis bullosa. Arch Dermatol. 2002;138(2):269–71.

    Article  PubMed  Google Scholar 

  37. Shimizu H, Hammami-Hauasli N, Hatta N, Nishikawa T, Bruckner-Tuderman L. Compound heterozygosity for silent and dominant glycine substitution mutations in COL7A1 leads to a marked transient intracytoplasmic retention of procollagen VII and a moderately severe dystrophic epidermolysis bullosa phenotype. J Invest Dermatol. 1999;113(3):419–21.

    Article  CAS  PubMed  Google Scholar 

  38. Hanson SG, Fine JD, Levy ML. Three new cases of transient bullous dermolysis of the newborn. J Am Acad Dermatol. 1999;40(3):471–6.

    Article  CAS  PubMed  Google Scholar 

  39. Hammami-Hauasli N, Raghunath M, Kuster W, Bruckner-Tuderman L. Transient bullous dermolysis of the newborn associated with compound heterozygosity for recessive and dominant COL7A1 mutations. J Invest Dermatol. 1998;111(6):1214–9.

    Article  CAS  PubMed  Google Scholar 

  40. Fassihi H, Diba VC, Wessagowit V, Dopping-Hepenstal PJ, Jones CA, Burrows NP, et al. Transient bullous dermolysis of the newborn in three generations. Br J Dermatol. 2005;153(5):1058–63.

    Article  CAS  PubMed  Google Scholar 

  41. Masunaga T, Shimizu H, Takizawa Y, Uitto J, Nishikawa T. Combination of novel premature termination codon and glycine substitution mutations in COL7A1 leads to moderately severe recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2000;114(1):204–5.

    Article  CAS  PubMed  Google Scholar 

  42. Kon A, Pulkkinen L, Ishida-Yamamoto A, Hashimoto I, Uitto J. Novel COL7A1 mutations in dystrophic forms of epidermolysis bullosa. J Invest Dermatol. 1998;111(3):534–7.

    Article  CAS  PubMed  Google Scholar 

  43. Terracina M, Posteraro P, Schubert M, Sonego G, Atzori F, Zambruno G, et al. Compound heterozygosity for a recessive glycine substitution and a splice site mutation in the COL7A1 gene causes an unusually mild form of localized recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 1998;111(5):744–50.

    Article  CAS  PubMed  Google Scholar 

  44. Baker AT, Ramshaw JAM, Chan D, Cole WG, Bateman JF. Changes in collagen stability and folding in lethal perinatal osteogenesis imperfecta. The effect of exl(I)-chain glycine-to-arginine substitutions. Biochem J. 1989;261:253–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Kon A, McGrath JA, Pulkkinen L, Nomura K, Nakamura T, Maekawa Y, et al. Glycine substitution mutations in the type VII collagen gene (COL7A1) in dystrophic epidermolysis bullosa: implications for genetic counseling. J Invest Dermatol. 1997;108(2):224–8.

    Article  CAS  PubMed  Google Scholar 

  46. Hashimoto I, Kon A, Tamai K, Uitto J. Diagnostic dilemma of “sporadic” cases of dystrophic epidermolysis bullosa: a new dominant or mitis recessive mutation? Exp Dermatol. 1999;8(2):140–2.

    Article  CAS  PubMed  Google Scholar 

  47. Rouan F, Pulkkinen L, Jonkman MF, Bauer JW, Cserhalmi-Friedman PB, Christiano AM, et al. Novel and de novo glycine substitution mutations in the type VII collagen gene (COL7A1) in dystrophic epidermolysis bullosa: implications for genetic counseling. J Invest Dermatol. 1998;111(6):1210–3.

    Article  CAS  PubMed  Google Scholar 

  48. Gardella R, Castiglia D, Posteraro P, Bernardini S, Zoppi N, Paradisi M, et al. Genotype-phenotype correlation in italian patients with dystrophic epidermolysis bullosa. J Invest Dermatol. 2002;119(6):1456–62.

    Article  CAS  PubMed  Google Scholar 

  49. Matsuba S, Suga Y, Mayuzumi N, Ikeda S, Ogawa H. A Japanese case of de novo dominant dystrophic epidermolysis bullosa. Clin Exp Dermatol. 2002;27(1):56–8.

    Article  CAS  PubMed  Google Scholar 

  50. Murata T, Masunaga T, Shimizu H, Takizawa Y, Ishiko A, Hatta N, et al. Glycine substitution mutations by different amino acids in the same codon of COL7A1 lead to heterogeneous clinical phenotypes of dominant dystrophic epidermolysis bullosa. Arch Dermatol Res. 2000;292(10):477–81.

    Article  CAS  PubMed  Google Scholar 

  51. Mecklenbeck S, Hammami-Hauasli N, Hopfner B, Schumann H, Kramer A, Kuster W, et al. Clustering of COL7A1 mutations in exon 73: implications for mutation analysis in dystrophic epidermolysis bullosa. J Invest Dermatol. 1999;112(3):398–400.

    Article  CAS  PubMed  Google Scholar 

  52. Kon A, Nomura K, Pulkkinen L, Sawamura D, Hashimoto I, Uitto J. Novel glycine substitution mutations in COL7A1 reveal that the Pasini and Cockayne-Touraine variants of dominant dystrophic epidermolysis bullosa are allelic. J Invest Dermatol. 1997;109(5):684–7.

    Article  CAS  PubMed  Google Scholar 

  53. Cserhalmi-Friedman PB, Grossman J, Karpati S, Ahmad W, Horvath A, Christiano AM. Identification of a de novo glycine substitution in the type VII collagen gene in a proband with mild dystrophic epidermolysis bullosa. Exp Dermatol. 1999;8(2):143–5.

    Article  CAS  PubMed  Google Scholar 

  54. Salas-Alanis JC, Amaya-Guerra M, McGrath JA. The molecular basis of dystrophic epidermolysis bullosa in Mexico. Int J Dermatol. 2000;39(6):436–42.

    Article  CAS  PubMed  Google Scholar 

  55. Murata T, Masunaga T, Ishiko A, Shimizu H, Nishikawa T. Differences in recurrent COL7A1 mutations in dystrophic epidermolysis bullosa: ethnic-specific and worldwide recurrent mutations. Arch Dermatol Res. 2004;295(10):442–7.

    Article  CAS  PubMed  Google Scholar 

  56. Csikos M, Szocs HI, Laszik A, Mecklenbeck S, Horvath A, Karpati S, et al. High frequency of the 425A—>G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa. Br J Dermatol. 2005;152(5):879–86.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Jinan Central Hospital, Jinan, China

    Ningning Dang MD

  2. Department of Dermatology, St. George Hospital, University of NSW Medical School, Sydney, NSW, Australia

    Dédée F. Murrell MA(Camb),BMBCh(Oxf),FAAD,MD,FACD,FRCP

Authors
  1. Ningning Dang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dédée F. Murrell MA(Camb),BMBCh(Oxf),FAAD,MD,FACD,FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dédée F. Murrell MA(Camb),BMBCh(Oxf),FAAD,MD,FACD,FRCP .

Editor information

Editors and Affiliations

  1. Department of Dermatology, St George Hospital, University of New South Wales, Sydney, New South Wales, Australia

    Dédée F. Murrell

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Dang, N., Murrell, D.F. (2015). COL7A1 and Its Role in Dystrophic Epidermolysis Bullosa. In: Murrell, D. (eds) Blistering Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45698-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-45698-9_11

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-45697-2

  • Online ISBN: 978-3-662-45698-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation