Genetics of progressive osseous heteroplasia

Progressive osseous heteroplasia (POH) is an autosomal dominant disorder, characterized by extensive dermal and muscular ossification during childhood and causes significant disability. In January 10 New England Journal of Medicine, Eileen Shore, and colleagues from University of Pennsylvania School of Medicine, Philadelphia, USA, show that POH is caused by a paternally inherited mutation of the GNAS1 gene — which controls the alpha subunit of the stimulatory G protein (G_sα) of adenylyl cyclase (NEJM 2002, 346:99-106).

Shore et al. used the polymerase chain reaction to amplify GNAS1 exons and exon–intron boundaries in 18 patients with sporadic or familial POH. In 13 of these patients they identified heterozygous inactivating GNAS1 mutations. The defective allele in POH was inherited exclusively from fathers, a result which is consistent with a model of imprinting for GNAS1.

Inactivating mutations in the GNAS1 gene inherited from mothers also caused...