Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations

Nat Rev Genet. 2009 Mar;10(3):173-83. doi: 10.1038/nrg2520.


Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. Mutations cause ECM dysfunction by combinations of two mechanisms. First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. Second, secretion of mutant protein can disturb crucial ECM interactions, structure and stability. Moreover, recent experiments suggest that endoplasmic reticulum (ER) stress, caused by mutant misfolded ECM proteins, contributes to the molecular pathology. Targeting ER stress might offer a new therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Connective Tissue Diseases / genetics*
  • Connective Tissue Diseases / metabolism
  • Endoplasmic Reticulum / metabolism
  • Extracellular Matrix / metabolism
  • Humans
  • Mutation*