Abstract
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 language | English |
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Pages (from-to) | 954-958 |
Number of pages | 5 |
Journal | Acta Dermato-Venereologica |
Volume | 96 |
Issue number | 7 |
DOIs | |
Publication status | Published - Nov 1 2016 |
Keywords
- Chronic skin ulcer
- Genodermatosis
- LAMB3
- Laminin EGF-like domain
- Protein folding
ASJC Scopus subject areas
- Dermatology