title: Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis.
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 alpha-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.
authors.affiliation: Molecular Pathophysiology Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892.
authors.forename: L S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: P V
authors.initials: PV
authors.lastname: Gejman
authors.forename: E
authors.initials: E
authors.lastname: Friedman
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: R M
authors.initials: RM
authors.lastname: Collins
authors.forename: E S
authors.initials: ES
authors.lastname: Gershon
authors.forename: A M
authors.initials: AM
authors.lastname: Spiegel
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D016368:Frameshift Mutation; D019204:GTP-Binding Proteins / Q000235:genetics*; D005796:Genes; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000138:chemical synthesis; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011547:Pseudohypoparathyroidism / Q000235:genetics*; D012016:Reference Values
chemical_list: D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D004247:DNA; D019204:GTP-Binding Proteins