COMPOUND HETEROZYGOSITY FOR AN OUT-OF-FRAME DELETION AND A SPLICE-SITE MUTATION IN THE LAMB3 GENE CAUSES NONLETHAL JUNCTIONAL EPIDERMOLYSIS-BULLOSA

Laminin-E 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 recessivel y inherited blistering disease of skin and mucous membranes. In this r eport, we describe a patient with a non-lethal variant of JEB who is a compound heterozygous for mutations affecting the LAMB3 gene. The pat ernally inherited mutation is a deletion of a single base (T) leading to a frameshift and premature termination codon. It results in mRNA de cay. The maternally inherited mutation is a G-->A transition at the la st 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 correc t splicing of LAMB3 pre-mRNA giving rise to two aberrant mRNA, in addi tion to the RNA transcript carrying the G-->A substitution. This resul t is compatible with the reduced expression of mutated laminin 5 molec ules with altered biological activity, and the mild JEB phenotype obse rved in the patient. (C) 1998 Academic Press.