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 |
|---|---|
| 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 |
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Keywords
- Chronic skin ulcer
- Genodermatosis
- LAMB3
- Laminin EGF-like domain
- Protein folding
ASJC Scopus subject areas
- Dermatology
Cite this
Structural defects of laminin β3 N-terminus underlie junctional epidermolysis bullosa with altered granulation tissue response. / El Hachem, May; Fortugno, Paola; Palmeri, Antonio; Helmer Citterich, Manuela; Diociaiuti, Andrea; Proto, Vittoria; Boldrini, Renata; Zambruno, Giovanna; Castiglia, Daniele.
In: Acta Dermato-Venereologica, Vol. 96, No. 7, 01.11.2016, p. 954-958.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural defects of laminin β3 N-terminus underlie junctional epidermolysis bullosa with altered granulation tissue response
AU - El Hachem, May
AU - Fortugno, Paola
AU - Palmeri, Antonio
AU - Helmer Citterich, Manuela
AU - Diociaiuti, Andrea
AU - Proto, Vittoria
AU - Boldrini, Renata
AU - Zambruno, Giovanna
AU - Castiglia, Daniele
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Chronic skin ulcer
KW - Genodermatosis
KW - LAMB3
KW - Laminin EGF-like domain
KW - Protein folding
UR - http://www.scopus.com/inward/record.url?scp=84992702758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992702758&partnerID=8YFLogxK
U2 - 10.2340/00015555-2439
DO - 10.2340/00015555-2439
M3 - Article
AN - SCOPUS:84992702758
VL - 96
SP - 954
EP - 958
JO - Acta Borealia
JF - Acta Borealia
SN - 0001-5555
IS - 7
ER -