Structural Defects of Laminin β3 N-terminus Underlie Junctional Epidermolysis Bullosa with Altered Granulation Tissue Response.
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 mis-folding 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.
Dermatology Division, Bambino Gesù Children's Hospital-IRCCS, P.zza Sant'Onofrio, 4, IT-00165 Rome, Italy.
Maya
M
El Hachem
Paola
P
Fortugno
Antonio
A
Palmeri
Manuela
M
Helmer-Citterich
Andrea
A
Diociaiuti
Vittoria
V
Proto
Renata
R
Boldrini
Giovanna
G
Zambruno
Daniele
D
Castiglia
D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D006097:Granulation Tissue; D006801:Humans; D008297:Male; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D000097794:Kalinin