Paternally Inherited Inactivating Mutations of the<i>GNAS1</i>Gene in Progressive Osseous Heteroplasia

Abstract

Paternally inherited inactivating GNAS1 mutations cause POH. This finding extends the range of phenotypes derived from haplo insufficiency of GNAS1, provides evidence that imprinting is a regulatory mechanism for GNAS1 expression, and suggests that Gsalpha is a critical negative regulator of osteogenic commitment in nonosseous connective tissues.