E210K MUTATION IN THE GENE ENCODING THE BETA-3 CHAIN OF LAMININ-5 (LAMB3) IS PREDICTIVE OF A PHENOTYPE OF GENERALIZED ATROPHIC BENIGN EPIDERMOLYSIS-BULLOSA

Pathogenetic mutations in the genes encoding the hemidesmosome-anchori ng filament complex proteins, laminin-5 and the 180 kDa bullous pemphi goid antigen, have been identified in patients with the inherited mech anobullous disease, junctional epidermolysis bullosa (EB). Furthermore , there is some evidence to suggest that precise definition of the nat ure of mutations in these genes may correlate to specific phenotypes o f disease, We report three junctional EB patients who carry an identic al missense mutation, E210K, on one allele of the gene encoding the be ta 3 subunit chain of laminin-5 (LAMB3) in addition to different nonse nse :mutations on the second allele, Two of the patients are adults an d display a specific phenotype of non-lethal junctional EB known as ge neralized 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 phen otype both in this child and in other junctional EB patients with the E210K mutation, Identification of this particular mutation has importa nt implications for clinical management and counselling.