Résumé
Perlecan is a proteoglycan present in all basement membranes with critical roles in several cell processes including basement membrane maintenance, cell adhesion properties, and regulation of growth factors signaling pathways. According to this large panel of functions, perlecan is associated to a complex series of physiological processes including cell proliferation, angiogenesis, endochondral ossification, neuromuscular excitability, and wound healing. Two rare and recessively inherited human disorders are associated with perlecan loss of function: the lethal dyssegmental dysplasia, SilvermanHandmaker type (DDSH), and the lifecompatible SchwartzJampel syndrome (SJS). Both are characterized by bone defects. Peripheral nerve hyperexcitability is also observed in SJS. A gene dosage effect accounts for the phenotypic difference between the two conditions. Investigations of animal models have demonstrated that they result from a combination of several structural and cell signaling defects on endochondral ossification and neuromuscular development as expected for the pleiotropic functions of this gigantic proteoglycan.