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Deficiency of the α‐Subunit of the Stimulatory G Protein and Severe Extraskeletal Ossification
Author(s) -
Eddy Mark C.,
Jan de beur Suzanne M.,
Yandow Suzanne M.,
McAlister William H.,
Shore Eileen M.,
Kaplan Frederick S.,
Whyte Michael P.,
Levine Michael A.
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.11.2074
Subject(s) - brachydactyly , gnas complex locus , ossification , medicine , pseudohypoparathyroidism , nonsense mutation , calcitonin , nonsense , parathyroid hormone , anatomy , endocrinology , pathology , missense mutation , mutation , genetics , biology , gene , short stature , calcium
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.