Abstract for presentation at 11th International Congress of Human Genetics

Chondrodysplasia are a heterogeneous group of disorders defined by a combination of clinical, radiological features and molecular-pathogenetic bases. Recent molecular advances have shown a wide variability of proteins involved in the skeletogenesis process including not only the orchestration of bone and cartilage components but also the influence of growth factors, receptors, hormones, cytokines and transcriptions factors. A significant number of chondrodysplasia are still defined on purely descriptive features and to identify their molecular bases, we have decided to use a strategy by autozygosity mapping. A clinical–radiological analysis has been first conducted to define homogenous samples allowing us to lump Stuve-Wiedemann syndrome and Schwartz-Jampel syndrome type 2, gloomy face syndrome and 3 M syndrome but also to split Desbuquois syndrome in two groups defined by the presence or not of typical hand anomalies. Based on international collaborations, we have collected the DNA samples of consanguineous families and using an autozygosity mapping strategy, we have first localized the disease locus gene and then identified mutations in genes encoding 1) components of the extracellular matrix (i.e. MATN3 and Spondylo-epi-metaphyseal dysplasia; ADAMTS10 and Weill-Marchesani syndrome) 2) receptor of cytokines (i.e. LIFR and Stuve-Wiedemann syndrome) 3) component of ubiquitin ligase complex (i.e. CUL7 and 3 M syndrome) 4) but also in gene encoding proteins of yet unknown function (i.e. Dymeclin and Dyggve-Melchior Clausen syndrome). Ongoing functional studies will hopefully lead to the understanding of the specific role of these proteins in enchondral ossification and skeletogenesis.