Type 2 autosomal dominant osteopetrosis is an inherited disorder characterized by osteosclerosis, end-plate thickening of the vertebrae and endobones. Although the disorder results in high bone mineral density, the bone is of poor quality and patients frequently present with fracture. Other features of the disease include nerve entrapment syndromes and osteomyelitis. Although the disorder is secondary to defects in osteoclast mediated bone resorption the pathophysiology of this disease has not been elucidated. The goals of the proposed investigations are to characterize type 2 autosomal dominant osteopetrosis and to identify the gene(s) responsible for this disorder using positional cloning techniques. Identification of the ADO2 gene(s) will provide substantial insight into the pathogenesis of ADO2 and to the basic biology of osteoclast function and regulation.
