Recent progress in the molecular genetics of sclerosing bone dysplasias

Bone mineral density is a quantitative trait influenced by both genetic and environmental factors. Epidemiological and twin studies have shown heritability for the variance of bone density of up to 80%. The role of genetic factors in bone homeostasis also is clearly illustrated by the existence of an extended group of genetic conditions associated with an abnormal bone density. These conditions are mainly monogenic in that they are caused by mutations in one gene. Recent developments in molecular genetics and genomics have resulted in a dramatically increased power to identify such disease-causing genes. The group of conditions with increased bone density has been poorly studied and understood at the molecular genetic level but recently for some of them, major breakthroughs have been made. These findings will make the molecular analysis of such patients an additional tool in diagnostics and in genetic counseling.