title: Progressive osseous heteroplasia caused by a novel nonsense mutation in the GNAS1 gene.
abstract: 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.
authors.affiliation: Department of Pediatrics, Tokyo Metropolitan Hachioji Children's Hospital, Hachioji, Japan. mgoto@chp.hachioji.tokyo.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Goto
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Mabe
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
mesh_terms: D002648:Child; D002864:Chromogranins; D018389:Codon, Nonsense; D018450:Disease Progression; D004550:Elbow / Q000473:pathology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D013006:Growth Hormone / Q000627:therapeutic use; D006365:Heel / Q000473:pathology; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D008297:Male; D009999:Ossification, Heterotopic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010290:Parents; D020641:Polymorphism, Single Nucleotide
chemical_list: D002864:Chromogranins; D018389:Codon, Nonsense; D019382:Human Growth Hormone; D013006:Growth Hormone; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs