Mosaicism in pseudoachondroplasia

Am J Med Genet. 1997 Jun 13;70(3):287-91.

Abstract

Pseudoachondroplasia (PSACH) is a spondylo-epi-metaphyseal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, and precocious osteoarthritis. PSACH is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene, which codes for a noncollagenous protein expressed in the territorial matrix of chondrocytes. Autosomal dominant inheritance has been demonstrated in many families; however, autosomal recessive inheritance has been suggested in some severe familial cases. Alternatively, germline/somatic mosaicism has been proposed and is credible, since it has been shown that dominantly inherited and sporadic cases of PSACH are caused by the same genetic defect. Here, we present evidence demonstrating somatic mosaicism in two PSACH families that were originally considered to represent autosomal recessive inheritance. The results of this study suggest that autosomal recessive inheritance is unlikely and all cases of PSACH should be studied for mutations in COMP.

Publication types

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

MeSH terms

  • Achondroplasia / genetics*
  • Amino Acid Sequence
  • Cartilage Oligomeric Matrix Protein
  • Child, Preschool
  • Extracellular Matrix Proteins*
  • Female
  • Genetic Linkage
  • Glycoproteins / genetics*
  • Humans
  • Male
  • Matrilin Proteins
  • Molecular Sequence Data
  • Mosaicism*
  • Pedigree

Substances

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