COMP is an extracellular calcium binding protein directly involved in chondrocyte migration and proliferation. It is observed at a high frequency in chondrocytes in developing bone and tendon. In<unk> , COMP is not secreted, but instead collects in the chondrocytes, ultimately poisoning and killing them. Though some chondrocytes do manage to survive, growth is significantly reduced, resulting in the characteristically short limbs and seemingly unaffected face and torso of those inflicted with the disorder (OMIM 2008). Mutations in COMP result in a phenotypic spectrum that varies from<unk>  (at the most extreme end) to multiple epiphyseal dysplasia or MED (a genetically similar, though milder skeletal dysplasia). Studies conducted by Hetch et al. suggest that type IX collagen, a collagen active specifically in the construction of cartilage, plays a key role in<unk> . The researchers found that IX collagen was amassed within the<unk>  chondrocytes. This discovery suggests that the pathogenesis of<unk>  involves the interactions of the mutant COMP gene products with specific cartilage components, such as type IX collagen, and that it is not solely the result of the effects of mutant molecules on the production and secretion of COMP (OMIM 2008). Molecular biology The COMP gene is located on chromosome 19p13.1; its precise locus is P49747. COMP contains 19 exons. The cartilage oligomeric matrix protein is 757 aa (OMIM 2008). COMP protein is found in the extracellular matrix, a complex web of proteins and other molecules that form in the spaces between the cells that make up ligaments and tendons. It is also found near chondrocytes (cartilage-forming cells). Chondrocytes play a vital role in osteogenesis (the formation of bone), particularly in the spine, hips, and limbs where osteogenesis begins with the formation of cartilage, which is then calcified and transformed into bone. We do not yet fully understand the normal function of COMP protein, though it is believed to play a part in cellular growth, division and apoptosis (self-destruction) of cells, as well as participating in the regulation of cell movement and attachment (OMIM 2008). Nearly 60 mutations in the COMP gene have been identified in individuals with<unk> . However, the mutation responsible for the most common allele is a deletion of one codon within a very short triplet repeat (GAC), in which the 469th amino acid, an aspartic acid, is deleted (OMIM 2008).
Pseudoachondroplasia
Achondroplasia
Rachischisis
Gastroschisis
Diaschisis
Omphalocele
Cranioschisis
Hypospadias