Structural defects of laminin β3 N-terminus underlie junctional epidermolysis bullosa with altered granulation tissue response

May El Hachem, Paola Fortugno, Antonio Palmeri, Manuela Helmer Citterich, Andrea Diociaiuti, Vittoria Proto, Renata Boldrini, Giovanna Zambruno, Daniele Castiglia

Research output: Contribution to journalArticle


Mutations in the laminin-332 (α3Aβ3γ2) genes cause junctional epidermolysis bullosa (JEB), a recessively inherited disease characterized by blistering and altered wound repair. In addition, specific mutations that affect the N-terminus of the α3A chain cause a JEB-related non-blistering condition characterized by chronic production of granulation tissue, suggesting a critical role of this region in epithelial-mesenchymal communication. We report here a 9-year-old patient with JEB with a few long-standing skin ulcers with prominent granulation tissue in the absence of active blistering. He bears a homozygous missense mutation, p.Gly254Asp, within the first laminin epidermal growth factor-like (LE) repeat of the β3 short arm. We show that p.Gly254Asp causes misfolding of the LE motif, leading to reduced secretion of laminin-332 and structural alterations of the cutaneous basement membrane zone. These findings demonstrate, in a patient in vivo, that the β3 short arm is also involved in the outcome of the granulation tissue response.

Original languageEnglish
Pages (from-to)954-958
Number of pages5
JournalActa Dermato-Venereologica
Issue number7
Publication statusPublished - Nov 1 2016



  • Chronic skin ulcer
  • Genodermatosis
  • LAMB3
  • Laminin EGF-like domain
  • Protein folding

ASJC Scopus subject areas

  • Dermatology

Cite this