Progressive osseous heteroplasia caused by a novel nonsense mutation in the GNAS1 gene.J Pediatr Endocrinol Metab. 2010 Mar; 23(3):303-9.JP
Progressive osseous heteroplasia (POH), characterized by progressive heterotopic ossifications of the dermis, skeletal muscle and deep connective tissues, is caused by inactivating mutations of GNAS1 of a paternally transmitted allele. We report a novel GNAS1 mutation in a patient with POH. The patient is a 6-year-old boy, whose short stature came to medical attention in infancy. He was diagnosed with growth hormone (GH) deficiency, and subsequent GH therapy resulted in catch-up growth. He developed soft tissue masses in the right heel and right elbow that were calcified or ossified on plain radiographs. MR imaging raised a suspicion of heterotopic ossification; thus, GNAS1 was analyzed. A novel nonsense mutation p.R342X was observed in the patient, but not in his parents. Single nucleotide polymorphism analysis revealed paternal transmission of the mutant allele. RT-PCR analysis demonstrated expression of both normal and mutant GNAS1 transcripts in the patient. Thus, the patient is considered to have developed POH because of the non-functioning truncated Gs(alpha) protein.