GENETIC-DISEASES OF THE EXTRACELLULAR-MATRIX - MORE THAN JUST CONNECTIVE-TISSUE DISORDER

The rapidly increasing knowledge about the molecular biology of the ex tracellular matrix has changed the concepts for the pathomechanisms of heritable connective tissue diseases. The spectrum of genetic matrix disorders is much broader than previously thought and now also include s diseases of organs such as the kidney, eye, and muscles. In addition , evidence is emerging that certain ''acquired'' diseases may be inher ited, and that defects in signal transduction and patterning genes con tribute to the pathology of connective tissue disorders. The phenotype s of genetic matrix disorders are determined by basic biological chara cteristics of the extracellular matrix. (a) The extracellular matrix o ccurs ubiquitously and is important for organ development and function s. (b) Matrix macromolecules are often large oligomers that polymerize into suprastructures at sever-al hierarchic levels. They form insolub le fibrils or filaments that are further assembled into tissue suprast ructures, for example, bundles or networks of fibrils. (c) Matrix supr astructures share characteristics with metal alloys. Tissue-specific m ixtures of matrix molecules form specific arrays that differ from thos e of the pure components. Therefore the phenotypes of matrix diseases reflect a cascade of pathological events disturbing alloy formation, s uch as abnormal protein synthesis and folding. defective fibrillogenes is, and bundling, all capable of leading to abnormal cell-matrix inter actions.