Deficiency of the α-subunit of the stimulatory G protein and severe extraskeletal ossification

Mark C. Eddy, Suzanne M. Jan de beur, Suzanne M. Yandow, William H. McAlister, Eileen M. Shore, Frederick S. Kaplan, Michael P. Whyte, Michael A. Levine

Research output: Contribution to journalArticlepeer-review

Abstract

Progressive osseous heteroplasia (POH) is a rare disorder characterized by dermal ossification beginning in infancy followed by increasing and extensive bone formation in deep muscle and fascia. We describe two unrelated girls with typical clinical, radiographic, and histological features of POH who also have findings of another uncommon heritable disorder, Albright hereditary osteodystrophy (AHO). One patient has mild brachydactyly but no endocrinopathy, whereas the other manifests brachydactyly, obesity, and target tissue resistance to thyrotropin and parathyroid hormone (PTH). Levels of the α-subunit of the G protein (G(s)α) were reduced in erythrocyte membranes from both girls and a nonsense mutation (Q12X) in exon 1 of the GNAS1 gene was identified in genomic DNA from the mildly affected patient. Features of POH and AHO in two individuals suggest that these conditions share a similar molecular basis and pathogenesis and that isolated severe extraskeletal ossification may be another manifestation of G(s)α deficiency.

Original languageEnglish (US)
Pages (from-to)2074-2083
Number of pages10
JournalJournal of Bone and Mineral Research
Volume15
Issue number11
DOIs
StatePublished - 2000

Keywords

  • Cyclic adenosine monophosphate
  • Heterotopic bone
  • Osteodystrophy
  • Pseudohypoparathyroidism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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