Abstract
Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by fragility of the skin and mucous membranes due to alterations in the dermal epidermal junction. This condition manifests as mechanically induced bullous lesions that heal with hypertrophic granulation tissue and/or atrophic scars. Here, we report two brothers carrying a homozygous LAMB3 missense variant, p.Gly254Asp, which affects the N-terminal end of the laminin-332 (LM332) β3 chain, previously described in another JEB family sharing a common ethnic origin and LAMB3 haplotype with the siblings reported here. Moreover, all affected patients with p.Gly254Asp mutation from both families exhibits a distinct phenotype consisting of a few localized long-standing skin lesions characterized by excessive granulation tissue formation or keloid scars, without new blistering, and associated with amelogenesis imperfecta. Our patients also showed nail dystrophy, expanding the phenotypic spectrum and confirming the peculiar role of the N-terminal end of the β3 chain in regulating the granulation tissue response associated with the wound healing process.