A heterozygous 4-bp deletion mutation in the Gsα gene (GNAS1) in a patient with albright hereditary osteodystrophy

Lee S. Weinstein, Pablo V. Gejman, Philippe de Mazancourt, Nadine American, Allen M. Spiegel

Research output: Contribution to journalArticle

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Abstract

Several heterozygous mutations within the gene encoding the α-subunit of Gs (GNAS1), the G protein that stimulates adenylyl cyclase, have been previously identified in patients with Albright hereditary osteodystrophy (AHO). We have now identified a fourth GNAS1 mutation from an AHO patient. Amplification by the polymerase chain reaction (PCR) of a genomic fragment encompassing GNAS1 exons 7 and 8 from one patient resulted in a product with aberrant migration on nondematuring polyacrylamide and agarose gels. Direct DNA sequencing identified a 4-bp deletion in one allele of exon 7 encoding a frameshift with a premature stop codon. Analysis of lymphocyte RNA by reverse transcription-PCR and direct sequencing showed that the GNAS1 allele bearing the mutation is not expressed as mRNA. Consistent with this, Northern analysis revealed an approximate 50% deficiency in steady-state levels of GNAS1 mRNA. These findings further illustrate the heterogeneity of GNAS1 gene defects in AHO.

Original languageEnglish (US)
Pages (from-to)1319-1321
Number of pages3
JournalGenomics
Volume13
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

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Sequence Deletion
Mutation
Exons
Alleles
Genes
Polymerase Chain Reaction
Messenger RNA
Nonsense Codon
DNA Sequence Analysis
GTP-Binding Proteins
Adenylyl Cyclases
Sepharose
Reverse Transcription
Lymphocytes
RNA
Albright's hereditary osteodystrophy

ASJC Scopus subject areas

  • Genetics

Cite this

A heterozygous 4-bp deletion mutation in the Gsα gene (GNAS1) in a patient with albright hereditary osteodystrophy. / Weinstein, Lee S.; Gejman, Pablo V.; de Mazancourt, Philippe; American, Nadine; Spiegel, Allen M.

In: Genomics, Vol. 13, No. 4, 1992, p. 1319-1321.

Research output: Contribution to journalArticle

Weinstein, Lee S. ; Gejman, Pablo V. ; de Mazancourt, Philippe ; American, Nadine ; Spiegel, Allen M. / A heterozygous 4-bp deletion mutation in the Gsα gene (GNAS1) in a patient with albright hereditary osteodystrophy. In: Genomics. 1992 ; Vol. 13, No. 4. pp. 1319-1321.
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