OSX/SP7 Mutations and Osteogenesis Imperfecta

Osteogenesis imperfecta or “brittle bone disease” is a collagen type I-related condition associated with osteoporosis and increased risk of bone fractures. Using a combination of homozygosity mapping and candidate gene approach we identified a homozygous single basepair deletion (c.1052delA) in SP7/Osterix (OSX) in a consanguineous patient with recessive osteogenesis imperfecta. The clinical findings of this patient include recurrent fractures, mild bone deformities, delayed tooth eruption, normal hearing, and white sclera. OSX encodes a transcription factor containing three Cys2-His2 zinc-finger DNA-binding domains at its C-terminus, which in mice has been shown to be essential for bone formation. The frameshift caused by the c.1052delA deletion removes the last 81 amino acids of the protein including the third zinc-finger motif. This finding adds a new locus to the spectrum of genes associated with osteogenesis imperfecta and reveals that SP7/OSX also plays a key role in human bone development.