Compound heterozygosity for an out-of-frame deletion and a splice site mutation in the LAMB3 gene causes nonlethal junctional epidermolysis bullosa

Biochem Biophys Res Commun. 1998 Feb 24;243(3):758-64. doi: 10.1006/bbrc.1998.8180.

Abstract

Laminin-5 is the major adhesion ligand of epithelial cells. Mutations in the genes encoding laminin-5 cause junctional epidermolysis bullosa (JEB), a clinically and genetically heterogeneous group of recessively inherited blistering disease of skin and mucous membranes. In this report, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The paternally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA decay. The maternally inherited mutation is a G-->A transition at the last base of exon 7 (628G-->A) which converts a codon for glutamic acid in a codon for lysine (E210K). The mutation 628G-->A alters the correct splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addition to the RNA transcript carrying the G-->A substitution. This result is compatible with the reduced expression of mutated laminin 5 molecules with altered biological activity, and the mild JEB phenotype observed in the patient.

Publication types

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

MeSH terms

  • Base Sequence
  • Blotting, Northern
  • Cell Adhesion Molecules / genetics*
  • Child, Preschool
  • Epidermolysis Bullosa, Junctional / genetics*
  • Fluorescent Antibody Technique
  • Gene Deletion*
  • Heterozygote*
  • Humans
  • Kalinin
  • Male
  • Mutation*
  • Pedigree
  • Polymerase Chain Reaction
  • RNA Precursors / chemistry
  • RNA Precursors / genetics
  • RNA Splicing*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • RNA-Directed DNA Polymerase

Substances

  • Cell Adhesion Molecules
  • RNA Precursors
  • RNA, Messenger
  • RNA-Directed DNA Polymerase