title: A heterozygous 4-bp deletion mutation in the Gs alpha gene (GNAS1) in a patient with Albright hereditary osteodystrophy.
abstract: Several heterozygous mutations within the gene encoding the alpha-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 nondenaturing 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.
authors.affiliation: Molecular Pathophysiology Branch, National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: L S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: P V
authors.initials: PV
authors.lastname: Gejman
authors.forename: P
authors.initials: P
authors.lastname: de Mazancourt
authors.forename: N
authors.initials: N
authors.lastname: American
authors.forename: A M
authors.initials: AM
authors.lastname: Spiegel
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002872:Chromosome Deletion; D004247:DNA; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D016368:Frameshift Mutation; D019204:GTP-Binding Proteins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011547:Pseudohypoparathyroidism / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D004247:DNA; D019204:GTP-Binding Proteins