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

P. Posteraro, S. Sorvillo, L. Gagnoux-Palacios, C. Angelo, M. Paradisi, G. Meneguzzi, D. Castiglia, G. Zambruno

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)758-764
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume243
Issue number3
DOIs
Publication statusPublished - Feb 24 1998

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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