Dyssegmental dysplasia, Silverman-Handmaker type, is caused by functional null mutations of the perlecan gene

Perlecan is a large heparan sulfate (HS) proteoglycan present in all basement membranes and in some other tissues such as cartilage1,2, and is implicated in cell growth and differentiation3,4,5. Mice lacking the perlecan gene6,7 (Hspg2) have a severe chondrodysplasia with dyssegmental ossification of the spine and show radiographic, clinical and chondro-osseous morphology similar to a lethal autosomal recessive disorder in humans termed...