Characterization of a de novo 43-bp deletion of the Gs[alpha] gene (GNAS1) in Albright hereditary osteodystrophy
Journal Article
·
· Genomics; (United States)
- Univ. of Leicester (United Kingdom)
- Univ. of Leicester (United Kingdom) Institute of Child Health, London (United Kingdom)
- Institute of Child Health, London (United Kingdom)
Albright hereditary osteodystrophy (AHO) is an autosomal dominant disorder characterized by short stature, obesity, mental retardation, subcutaneous calcification, and brachy-metaphalangia. Two distinct forms of AHO exist; pseudohypoparathyroidism type I (PHPI) and pseudopseudohypoparathyrodism (PPHP). The classification is dependent upon the presence or absence, respectively, of resistance to parathyroid and other hormones that bind to Gs-protein-coupled membrane receptors stimulating adenylyl cyclase. Gs is a heterotrimeric protein comprising [alpha], [beta], and [gamma]-subunits encoded by separate genes. Genomic DNA was isolated from peripheral leukocytes from 13 unrelated AHO patients. Exon 4 and flanking intronic sequence of GNAS1 were PCR amplified. A single PCR product corresponding to the expected 159-bp fragment was identified in 12 affected individuals with either PHPIa or PPHP. In patient 10285 an additional smaller fragment was detected but was not present in either of the unaffected parents. These two fragments were isolated from a 2% agarose gel. Direct sequencing of the smaller fragment revealed a 43-bp deletion comprising at least 35 hp of the 3[prime] end of exon 4 and the donor splice site of intron 4 and extending into the following intro. The 43-bp deletion would lead to a premature stop codon, 62 codons downstream of the deletion. The de novo mutation reported here is the largest deletion in the Gs[alpha] gene described so far for AHO patients.
- OSTI ID:
- 6872182
- Journal Information:
- Genomics; (United States), Journal Name: Genomics; (United States) Vol. 21:2; ISSN GNMCEP; ISSN 0888-7543
- Country of Publication:
- United States
- Language:
- English
Similar Records
Deletion mutations of the Bs-alpha gene in patients with Albright hereditary osteodystrophy: Possible mutation hot-spot in exon 7
Albright hereditary osteodystrophy and del(2)(q37.3) in four unrelated individuals
Genetic deficiency of the. cap alpha. subunit of the guanine nucleotide-binding protein G/sub s/ as the molecular basis for Albright hereditary osteodystrophy
Journal Article
·
Thu Sep 01 00:00:00 EDT 1994
· American Journal of Human Genetics
·
OSTI ID:134777
Albright hereditary osteodystrophy and del(2)(q37.3) in four unrelated individuals
Journal Article
·
Mon Jul 31 00:00:00 EDT 1995
· American Journal of Medical Genetics
·
OSTI ID:441150
Genetic deficiency of the. cap alpha. subunit of the guanine nucleotide-binding protein G/sub s/ as the molecular basis for Albright hereditary osteodystrophy
Journal Article
·
Thu Dec 31 23:00:00 EST 1987
· Proc. Natl. Acad. Sci. U.S.A.; (United States)
·
OSTI ID:6142342