Genetic deficiency of the. cap alpha. subunit of the guanine nucleotide-binding protein G/sub s/ as the molecular basis for Albright hereditary osteodystrophy

Journal Article · Fri Jan 01 04:00:00 EST 1988 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.85.2.617· OSTI ID:6142342

Levine, M A; Ahn, T G; Klupt, S F; Kaufman, K D; Smallwood, P M; Bourne, H R; Sullivan, K A; Van Dop, C

Patients who have pseudohypoparathyroidism type I associated with Albright hereditary osteodystrophy commonly have a genetic deficiency of the ..cap alpha.. subunit of the G protein that stimulated adenylyl cyclase ..cap alpha..G/sub s/. To discover the molecular mechanism that causes ..cap alpha..G/sub s/ deficiency in these patients, the authors examined eight kindreds with one or more members affected with Albright hereditary osteodystrophy or pseudohypoparathyroidism and ..cap alpha..G/sub s/ deficiency. In these families, ..cap alpha..G/sub s/, deficiency and the Albright hereditary osteodystrophy phenotype were transmitted together in a dominant inheritance pattern. Using a cDNA hybridization probe for ..cap alpha..G/sub s/, restriction analysis with several analysis with several endonucleases showed no abnormalities of restriction fragments or gene dosage. RNA blot and dot blot analysis of total RNA from cultured fibroblasts obtained from the patients revealed approx. 50% reduced mRNA levels for ..cap alpha..G/sub s/ in affected members of six of the pedigrees but normal levels in affected members of the two other pedigrees, compared to mRNA levels in fibroblasts from unaffected individuals. By contrast, mRNA levels encoding the ..cap alpha.. subunit of the G protein that inhibits adenylyl cyclase were not altered. These findings suggest that several molecular mechanisms produce ..cap alpha..G/sub s/ deficiency in patients with pseudohypoparathyroidism type Ia and that major gene rearrangements or deletions are not a common cause for ..cap alpha..G/sub s/ deficiency in pseudohypoparathyroidism type I.

• Research Organization: Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA)
• OSTI ID: 6142342
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 85:2; ISSN PNASA
• Country of Publication: United States
• Language: English

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550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
ENDOCRINE DISEASES
ENDOCRINE GLANDS
ENZYMES
FIBROBLASTS
GLANDS
HEREDITARY DISEASES
HYBRIDIZATION
ISOTOPES
LIGHT NUCLEI
LYASES
MESSENGER-RNA
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARATHYROID GLANDS
PATHOGENESIS
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PROTEINS
RADIOISOTOPES
RECOMBINANT DNA
RNA
SOMATIC CELLS