J Med Genet 44:181-192 doi:10.1136/jmg.2006.045302
  • Original article

Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes

  1. Roslyn Varki,
  2. Sara Sadowski,
  3. Jouni Uitto,
  4. Ellen Pfendner
  1. DebRA Molecular Diagnostics Laboratory, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
  1. Correspondence to:
 J Uitto
 Department of Dermatology and Cutaneous Biology, Jefferson Medical College, 233 South 10th Street, Suite 450 BLSB, Philadelphia, PA 19107, USA; Jouni.Uitto{at}
  • Received 11 July 2006
  • Accepted 17 August 2006
  • Revised 11 August 2006
  • Published Online First 13 September 2006


Background: The dystrophic forms of epidermolysis bullosa (DEB), a group of heritable blistering disorders, show considerable phenotypic variability, and both autosomal dominant and autosomal recessive inheritance can be recognised. DEB is derived from mutations in the type VII collagen gene (COL7A1), encoding a large collagenous protein that is the predominant, if not exclusive, component of the anchoring fibrils at the dermal–epidermal junction.

Methods: The Dystrophic Epidermolysis Bullosa Research Association Molecular Diagnostics Laboratory (Philadelphia, Pennsylvania, USA), established in 1996, has analysed more than 1000 families with different forms of epidermolysis bullosa, among them 332 families with DEB. DNA specimens were subjected to mutation analysis by polymerase chain reaction (PCR) amplification of all 118 exons and flanking intronic sequences of COL7A1, followed either by heteroduplex scanning and sequencing of the PCR products demonstrating heteroduplexes or by direct nucleotide sequencing.

Results: 355 mutant alleles out of the anticipated 438 (81.1%) were disclosed. Among these mutations, a total of 242 mutations were distinct and 138 were novel, previously unreported mutations. No evidence of mutations in any other gene was obtained.

Discussion: Examination of the mutation database suggested phenotype–genotype correlations, contributing to the improved subclassification of DEB with prognostic implications. The mutation information also forms the basis for accurate genetic counselling and prenatal diagnosis in families at risk for recurrence.


  • Published Online First 13 September 2006

  • Funding: This study was financially supported by the DebRA of America and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health Grant P01 AR38923.

  • Competing interests: None declared.