Mutations of the Gs α-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis

Lee S. Weinstein, Pablo V. Gejman, Eitan Friedman, Takashi Kadowaki, Regina M. Collins, Elliot S. Gershon, Allen M. Spiegel

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

Abstract

Affected members of most kindreds with Albright hereditary osteodystrophy have a partial deficiency of functional Gs, the guanine nucleotide-binding protein that stimulates adenylyl cyclase. By use of the polymerase chain reaction to amplify genomic fragments with the attachment of a high-melting G+C-rich region (GC clamp) and analysis of these fragments by denaturing gradient gel electrophoresis, heterozygous mutations in the Gs α-subunit gene were found in two kindreds. These included a G → C substitution at the donor splice junction of intron 10 and a coding frameshift created by a single base deletion within exon 10. The findings illustrate the heterogeneity of genetic defects in Albright hereditary osteodystrophy and the usefulness of the polymerase chain reaction-denaturing gradient gel electrophoresis method to search rapidly for mutations in a large candidate gene.

Original languageEnglish (US)
Pages (from-to)8287-8290
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number21
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • Heterotrimeric guanine nucleotide-binding protein
  • Polymerase chain reaction
  • Pseudohypoparathyroidism
  • Splice junction

ASJC Scopus subject areas

  • General

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