Pseudoachondroplasia and multiple epiphyseal dysplasia: mutation review, molecular interactions, and genotype to phenotype correlations

Hum Mutat. 2002 May;19(5):465-78. doi: 10.1002/humu.10066.


Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) constitute a bone dysplasia family, which is both genetically and phenotypically heterogeneous. The disease spectrum ranges from mild MED, which manifests with pain and stiffness in the joints and delayed and irregular ossification of the epiphyses, to the more severe PSACH, which is characterized by marked short stature, deformity of the legs, and ligamentous laxity. PSACH is almost exclusively caused by mutations in cartilage oligomeric matrix protein (COMP) whereas various forms of MED are caused by mutations in the genes encoding COMP, type IX collagen (COL9A1, COL9A2, and COL9A3), matrilin-3 (MATN3), and solute carrier member 26, member 2 gene (SLC26A2). In this review we discuss specific disease-causing mutations and the clustering of these mutations in functionally and structurally important regions of the respective gene products, genotype to phenotype correlations, and the diagnostic relevance of mutation screening in these osteochondrodysplasias.

Publication types

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

MeSH terms

  • Achondroplasia / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Cartilage Oligomeric Matrix Protein
  • Collagen Type IX / genetics
  • Extracellular Matrix Proteins / genetics
  • Genotype
  • Glycoproteins / genetics
  • Humans
  • Matrilin Proteins
  • Molecular Sequence Data
  • Mutation / genetics*
  • Osteochondrodysplasias / genetics*
  • Phenotype


  • Cartilage Oligomeric Matrix Protein
  • Collagen Type IX
  • Extracellular Matrix Proteins
  • Glycoproteins
  • Matrilin Proteins
  • TSP5 protein, human