Novel Premature Termination Codon Mutations in the Laminin γ2-Chain Gene (LAMC2) in Herlitz Junctional Epidermolysis Bullosa

Herlitz junctional epidermolysis bullosa (H-JEB), a severe blistering disorder affecting the skin and a variety of extracutaneous epithelia, leads to premature demise of the affected individuals during early postnatal period (Fine et al. 1991). A pathogenetic ultrastructural feature of the skin of affected individuals is abnormalities in hemidesmosome/anchoring filament complexes, associated with tissue separation within the lamina lucida at the dermal–epidermal basement membrane zone (Tidman & Eady 1986). A characteristic immunofluorescence finding is absent expression of laminin 5, a member of the laminin family of proteins, which consists of three polypeptides, the 3, 3, and 2 chains (Aumailley & Krieg 1996). Since all three chains are required for stable assembly of trimeric laminin 5 molecules, the corresponding genes, LAMA3, LAMB3, and LAMC2, serve as potential candidate genes for mutations in H-JEB. In fact, a number of distinct mutations in these three genes have been demonstrated in patients with H-JEB, all mutations resulting in premature termination codons. Interestingly, however, the majority of the mutations (80%) reside in the LAMB3 genes, with only a few of them having been reported in the LAMA3 or LAMC2 genes (Pulkkinen et al. 1999).