The genetics of dominant osteopetrosis

Autosomal dominant osteopetroses (ADO) are classically divided into two types, ADOI and ADOII, which are differentiated according to the main sites of osteosclerosis localization. For ADOI this is the cranial vault and, for ADOII, the spine, pelvis and skull base. ADOII patients are heterozygous for a mutation in the ClCN7 gene, coding for a putative chloride channel; ADOI patients are heterozygous for mutations in the LRP5 gene, a Wnt coreceptor, which affects osteoblast function. This second finding challenges the old assumption that osteopetroses are always due to an osteoclast defect in bone resorption.