Research on Skeletal Dysplasias

The objectives of ESDN-Research are to understand comprehensively the molecular genetics and cell-matrix pathophysiology of skeletal dysplasias. The extremely complex and heterogeneous presentation of these diseases requires an integrated multidisciplinary research approach. In this respect the overall methodology of this project consists of three integral components:

  • Patient ascertainment and comprehensive clinical and radiographic diagnosis.
    The ascertainment and correct diagnosis of individuals with skeletal dysplasias is fundamental to the success of this project. Each of the network partners has individual experience of this with particular skills in their specific area of interest. The development of uniform criteria for radiographic diagnosis will be provided by the expert radiologists within the partnership.
  • Molecular genetics and genetic heterogeneity.
    The use of unique sources of novel human bone and cartilage cDNAs, together with clinical material and mouse data, will generate a number of positional and functional candidate genes for skeletal dysplasias. In addition, genetic linkage analysis remains a very powerful technique for rapidly identifying a sub-chromosomal location of a particular disease gene and using suitable families, we intend to fully exploit the recent technological advances in this approach.
  • Molecular cell pathology and matrix structure/function relationships.
    Proteomics allows the identification and comparative analysis of proteins expressed by cells or tissues. This approach is suited for identifying groups of proteins associated with specific higher-molecular structures or pathways, and how such patterns are perturbed as a result of pathological changes. Furthermore, the development of biomolecular techniques now makes it possible to study in high resolution the structural and functional properties of proteins and investigate the effects of mutations. The development of in vitro expression systems allows the production of large quantities of biologically active recombinant protein that can be engineered to contain disease mutations.

ESDN-Research continues under the project title EuroGrow "Pathophysiology of the Cartilage Growth Plate".