title: Laminins and human disease.
abstract: The laminin protein family has diverse tissue expression patterns and is involved in the pathology of a number of organs, including skin, muscle, and nerve. In the skin, laminins 5 and 6 contribute to dermal-epidermal cohesion, and mutations in the constituent chains result in the blistering phenotype observed in patients with junctional epidermolysis bullosa (JEB). Allelic heterogeneity is observed in patients with JEB: mutations that results in premature stop codons produce a more severe phenotype than do missense mutations. Gene therapy approaches are currently being studied in the treatment of this disease. A blistering phenotype is also observed in patients with acquired cicatricial pemphigoid (CP). Autoantibodies targeted against laminins 5 and 6 destabilize epithelial adhesion and are pathogenic. In muscle cells, laminin alpha 2 is a component of the bridge that links the actin cytoskeleton to the extracellular matrix. In patients with laminin alpha 2 mutations, the bridge is disrupted and mature muscle cells apoptose. Congenital muscular dystrophy (CMD) results. The role of laminin in diseases of the nervous system is less well defined, but the extracellular protein has been shown to serve an important role in peripheral nerve regeneration. The adhesive molecule influences neurite outgrowth, neural differentiation, and synapse formation. The broad spatial distribution of laminin gene products suggests that laminin may be involved in a number of diseases for which pathogenic mechanisms are still being unraveled.
authors.affiliation: Department of Genetics, M-344, School of Medicine, Stanford University, Stanford, California 94305, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: McGowan
authors.forename: M P
authors.initials: MP
authors.lastname: Marinkovich
mesh_terms: D000483:Alleles; D018388:Codon, Terminator; D004820:Epidermolysis Bullosa / Q000503:physiopathology; D015316:Genetic Therapy; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D009136:Muscular Dystrophies / Q000503:physiopathology; D009154:Mutation; D010390:Pemphigoid, Benign Mucous Membrane / Q000503:physiopathology; D010525:Peripheral Nerves / Q000503:physiopathology; D012038:Regeneration
chemical_list: D018388:Codon, Terminator; D007797:Laminin