Genetic Disorders of the Extracellular Matrix: From Cell and Gene Therapy to Future Applications in Regenerative Medicine

Annu Rev Genomics Hum Genet. 2022 Aug 31:23:193-222. doi: 10.1146/annurev-genom-083117-021702. Epub 2022 May 10.


Metazoans have evolved to produce various types of extracellular matrix (ECM) that provide structural support, cell adhesion, cell-cell communication, and regulated exposure to external cues. Epithelial cells produce and adhere to a specialized sheet-like ECM, the basement membrane, that is critical for cellular homeostasis and tissue integrity. Mesenchymal cells, such as chondrocytes in cartilaginous tissues and keratocytes in the corneal stroma, produce a pericellular matrix that presents optimal levels of growth factors, cytokines, chemokines, and nutrients to the cell and regulates mechanosensory signals through specific cytoskeletal and cell surface receptor interactions. Here, we discuss laminins, collagen types IV and VII, and perlecan, which are major components of these two types of ECM. We examinegenetic defects in these components that cause basement membrane pathologies such as epidermolysis bullosa, Alport syndrome, rare pericellular matrix-related chondrodysplasias, and corneal keratoconus and discuss recent advances in cell and gene therapies being developed for some of these disorders.

Keywords: Alport syndrome; chondrodysplasia; collagens; epidermolysis bullosa; laminins; perlecan.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cornea / metabolism
  • Cornea / pathology
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Matrix* / genetics
  • Extracellular Matrix* / metabolism
  • Genetic Therapy
  • Humans
  • Regenerative Medicine*


  • Extracellular Matrix Proteins