Altered laminin 5 expression due to mutations in the gene encoding the beta 3 chain (LAMB3) in generalized atrophic benign epidermolysis bullosa.
The anchoring filament component laminin 5 (kalinin/nicein) is a candidate protein for mutations in some hereditary blistering skin disorders. In this study, laminin 5 expression was assessed in a family with generalized atrophic benign epidermolysis bullosa, a non-lethal variant of the junctional form of epidermolysis bullosa. Immunofluorescence microscopy of the skin basement-membrane zone with a monoclonal antibody (GB3) revealed reduced anti-laminin 5 staining compared to normal controls. The labeling, when examined by immunoelectron microscopy, was present within the lower lamina lucida, immediately below the plane of blister formation. Numerous hemidesmosomes and well-formed anchoring filaments were seen on transmission electron microscopy. Polymerase chain reaction amplification of genomic DNA encoding the beta 3 subunit (LAMB3) of laminin 5, heteroduplex analysis of the polymerase chain reaction products, and nucleotide sequencing of the heteroduplexes revealed two putative mutations within the LAMB3 gene; these consisted of a premature termination codon in exon 3 and a missense mutation in exon 7. Exons 3 and 7 encode part of domain VI of the laminin 5 beta 3 chain short arm. This globular domain of the protein has been postulated to have an important function in the interaction of laminin 5 with other structural components of the basement membrane zone, such as laminin 6 (K-laminin). Thus the mutations delineated in this family may have a critical pathogenetic significance in reducing adhesion between the epidermis and the dermis.
McGrath
J A
JA
Department of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Pulkkinen
L
L
Christiano
A M
AM
Leigh
I M
IM
Eady
R A
RA
Uitto
J
J
D001483:Base Sequence; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation
D007797:Laminin