title: Molecular basis of clinical heterogeneity in the Ehlers-Danlos syndrome.
abstract: Mutations which give rise to the many different phenotypes of the Ehlers-Danlos syndrome affect both collagen and noncollagen genes but, ultimately, affect the function of the major collagens in tissues. The precise phenotypic findings depend on the nature of the defect, and the phenotypic changes attributable to a single mutation have a relatively limited extent of variability. Analyses of these mutants have led to an increased understanding of the role of lysyl hydroxylation in collagen function, of the role of type III collagen in tissue integrity, and have emphasized the role of trace metals in collagen metabolism. A more complete understanding of these disorders will require identification of the mutations responsible for the dominant and X-linked EDS phenotypes, using classical linkage analysis with restriction fragment length polymorphisms from candidate genes, and detailed biochemical study of cells in culture from these patients. For the mutations which affect the type III collagen genes, it will be important to identify the regions of the mutations and to sequence the mRNA or genes involved in order to understand how the mutations affect the intracellular and extracellular handling of the molecules. Study of these molecules could have important implications for understanding the molecular and cell biology of collagen secretion specifically, and protein processing and secretion in general. Similarly, identification and characterization of the other mutations which result in the EDS phenotypes will lead to increased understanding of the nature of interactions of a variety of macromolecules in the extracellular matrix, of the control of their synthesis, of their roles in tissue development, and of the manner in which their gene expression is controlled.
mesh_terms: D003094:Collagen / Q000378:metabolism*; D004535:Ehlers-Danlos Syndrome / Q000145:classification / Q000235:genetics*; D005796:Genes; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: D003094:Collagen