A HOMOZYGOUS NONSENSE MUTATION IN THE BETA-3 CHAIN GENE OF LAMININ-5 (LAMB3) IN HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA

Herlitz junctional epidermolysis bullosa (H-JEB) is a severe autosomal recessive disorder characterized by blister formation within the dermal-epidermal basement membrane, Based on immunofluorescence analysis recognizing laminin 5 epitopes (previously known as nicein/kalinin), the genes for this lamina lucida protein have been proposed as candidate genes in H-JEB. In this study, we examined the gene encoding the beta 3 polypeptide chain of laminin 5 (LAMB3) by Northern hybridization and RT-PCR analysis of keratinocyte mRNA from a proband in a family with H-JEB. Northern analysis revealed markedly reduced levels of the laminin beta 3 chain mRNA. Amplification of mRNA by RT-PCR, followed by direct nucleotide sequencing, revealed a homozygous C-to-T transition resulting in a premature termination codon (CGA --> TGA) on both alleles, This mutation was verified at the genomic DNA level, and both parents were shown to be heterozygous carriers of the same mutation. This is the first description of a mutation in the laminin beta 3 chain gene an H-JEB patient. (C) 1994 Academic Press, Inc.