A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in Hallopeau-Siemens dystrophic epidermolysis bullosa

Nat Genet. 1993 Nov;5(3):287-93. doi: 10.1038/ng1193-287.


The Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a life-threatening autosomal disease characterized by loss of dermal-epidermal adherence with abnormal anchoring fibrils (AF). We recently linked HS-RDEB to the type VII collagen gene (COL7A1) which encodes the major component of AF. We describe a patient who is homozygous for an insertion-deletion in the FN-4A domain of the COL7A1 gene. This defect causes a frameshift mutation which leads to a premature stop codon in the FN-5A domain, resulting in a marked diminution in mutated mRNA levels, with no detectable type VII collagen polypeptide in the patient. Our data suggest strongly that this null allele prevents normal anchoring fibril formation in homozygotes and is the underlying cause of HS-RDEB in this patient.

Publication types

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

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Child, Preschool
  • Collagen / genetics*
  • DNA Transposable Elements*
  • DNA, Complementary
  • Epidermolysis Bullosa Dystrophica / genetics*
  • Epidermolysis Bullosa Dystrophica / pathology
  • Fluorescent Antibody Technique
  • Humans
  • Male
  • Microscopy, Electron
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Polymorphism, Genetic
  • Sequence Deletion*
  • Skin / pathology
  • Skin / ultrastructure


  • DNA Transposable Elements
  • DNA, Complementary
  • Collagen