Hereditary skin diseases of anchoring fibrils

J Dermatol Sci. 1999 Jun;20(2):122-33. doi: 10.1016/s0923-1811(99)00018-3.


Remarkable progress has been made in the last few years in understanding the functions of the anchoring fibrils, polymers of collagen VII, that connect the epidermal basement membrane with the dermal connective tissue. Novel insights into the biology of these fibrils have been gained from studies on dystrophic epidermolysis bullosa (DEB), a group of inherited blistering disorders caused by abnormalities of the anchoring fibrils. Mutations in the COL7A1 gene encoding collagen VII have been disclosed in a number of DEB families, and the mutation analyses and studies on genotype-phenotype correlations in DEB have revealed an unusual complexity of the gene defects and their biological consequences. In analogy to heritable disorders of other collagen genes, predictable phenotypes of COL7A1 mutations causing premature termination codons (PTC) or dominant negative interference have been observed. However, collagen VII seems to be unique among collagens in that many mutations lead to minimal phenotypes, or to no phenotype at all. Furthermore, the mild DEB phenotypes can be severely modulated by a second mutation in individuals compound heterozygous for two different COL7A1 defects. Therefore, not only definition of mutations with diagnostic analyses, but also cell biological, protein chemical and suprastructural studies of the mutated molecules are required for understanding the pathomechanisms underlying DEB.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basement Membrane / chemistry
  • Basement Membrane / pathology
  • Collagen / chemistry
  • Collagen / genetics
  • Epidermolysis Bullosa Dystrophica / genetics*
  • Epidermolysis Bullosa Dystrophica / metabolism*
  • Epidermolysis Bullosa Dystrophica / pathology
  • Humans
  • Infant, Newborn
  • Skin / chemistry*
  • Skin / pathology


  • Collagen