Identification of two splicing mutations in the collagen type VII gene (COL7A1) of a patient affected by the localisata variant of recessive dystrophic epidermolysis bullosa

Am J Hum Genet. 1996 Aug;59(2):292-300.

Abstract

Collagen type VII gene (COL7A1) has been demonstrated to be altered in several variants of dystrophic epidermolysis bullosa (DEB), with either recessive or dominant mode of inheritance. We have identified two mutations in a patient affected by a localisata variant of recessive DEB (L-RDEB), which is characterized by the less severe phenotype of the syndrome. These mutations are the first splicing mutations so far described for COL7A1 in DEB. One mutation is a paternally inherited A-->G transition at position -2 of the donor splicing site of intron 3, which results in three aberrant mRNAs, depending on the skipping of exon 3, the usage of a cryptic donor site inside exon 3, or the maintenance of intron 3. The second mutation is a maternally inherited G-->A transition at position -1 of the donor splicing site of intron 95, which induces the activation of a cryptic donor site 7 nt upstream the normal site and gives rise to a deleted mRNA, in addition to the normal one. All aberrant mRNAs show a shift of the reading frame, thus generating premature termination codons of translation. Allele-specific analysis of the transcripts has shown that the maternal mutation does not completely abolish the correct splicing of COLVII pre-mRNA, thus allowing, in the patient, the synthesis of a certain level of a functional protein. This result is compatible with the mild clinical L-RDEB phenotype observed in our patient.

Publication types

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

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Base Sequence
  • Biopsy
  • Collagen / genetics*
  • Epidermolysis Bullosa Dystrophica / epidemiology
  • Epidermolysis Bullosa Dystrophica / genetics*
  • Female
  • Genes, Recessive*
  • Humans
  • Italy / epidemiology
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics
  • Sequence Analysis, DNA
  • Skin / pathology

Substances

  • RNA, Messenger
  • Collagen