E210K mutation in the gene encoding the β3 chain of laminin-5 (LAMB3) is predictive of a phenotype of generalized atrophic benign epidermolysis bullosa

Pathogenetic mutations in the genes encoding the hemidesmosome- anchoring filament complex proteins, laminin-5 and the 180 kDa bullous pemphigoid antigen, have been identified in patients with the inherited mechanobullous disease, junctional epidermolysis bullosa (EB). Furthermore, there is some evidence to suggest that precise definition of the nature of mutations in these genes may correlate to specific phenotypes of disease. We report three junctional EB patients who carry an identical missense mutation, E210K, on one allele of the gene encoding the β3 subunit chain of laminin-5 (LAMB3) in addition to different nonsense mutations on the second allele. Two of the patients are adults and display a specific phenotype of non-lethal junctional EB known as generalized atrophic benign EB, which is associated with trauma-induced blisters, nail dystrophy and alopecia. As the third patient is a young child with fewer features of this subtype to date, identification of E210K in combination with a nonsense LAMB3 mutation may be predictive of the subsequent development of a generalized atrophic benign EB phenotype both in this child and in other junctional EB patients with the E210K mutation. Identification of this particular mutation has important implications for clinical management and counselling.