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 language | English (US) |
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Pages (from-to) | 8287-8290 |
Number of pages | 4 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 87 |
Issue number | 21 |
DOIs | |
State | Published - 1990 |
Externally published | Yes |
Keywords
- Heterotrimeric guanine nucleotide-binding protein
- Polymerase chain reaction
- Pseudohypoparathyroidism
- Splice junction
ASJC Scopus subject areas
- General