{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:43:50Z","timestamp":1789447430790,"version":"build-2803163510"},"reference-count":38,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Objective: The GNAS gene encodes the \u03b1-subunit of stimulatory G proteins, which play a crucial role in intracellular signal transduction of peptide and neurotransmitter receptors. In addition to transcript variants that differ in their first exon due to different promoters, there are two long (Gs\u03b1-L) and two short (Gs\u03b1-S) splice variants, created by alternative splicing. Heterozygous inactivating maternally inherited mutations of GNAS lead to a phenotype in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type Ia.<\/jats:p>\n                  <jats:p>Methods and Results: The GNAS gene of a 10-yr-old girl with brachymetacarpia, mental retardation, normocalcemic pseudohypoparathyroidism, and hypothyroidism was investigated. We found a heterozygous insertion of an adenosine in exon 3 altering codon 85 and leading to a frame shift inducing a stop codon in exon 4. Molecular studies of cDNA from blood RNA demonstrated normal, biallelic expression of Gs\u03b1-S transcripts, whereas expression of Gs\u03b1-L transcripts from the maternal allele was reduced. Immunoblot analysis revealed a reduced Gs\u03b1-L protein level to about 50%, whereas the protein level of Gs\u03b1-S was unaltered. Furthermore, the Gs\u03b1 protein activity in erythrocyte membranes was diminished to about 75% of normal. Both the reduced activity and the mutation were also found in the mother and the affected younger brother.<\/jats:p>\n                  <jats:p>Conclusion: This report demonstrates the first evidence for a pathogenic mutation in exon 3 of the GNAS gene. The mutation is associated with a phenotype of Albright hereditary osteodystrophy and pseudohypoparathyroidism type Ia due to selective deficiency of Gs\u03b1-L and a partial reduction of Gs\u03b1 activity.<\/jats:p>","DOI":"10.1210\/jc.2006-2122","type":"journal-article","created":{"date-parts":[[2007,2,13]],"date-time":"2007-02-13T21:57:43Z","timestamp":1171403863000},"page":"1764-1768","source":"Crossref","is-referenced-by-count":33,"title":["A Disruptive Mutation in Exon 3 of the GNAS Gene with Albright Hereditary Osteodystrophy, Normocalcemic Pseudohypoparathyroidism, and Selective Long Transcript Variant Gs\u03b1-L Deficiency"],"prefix":"10.1210","volume":"92","author":[{"given":"Susanne","family":"Thiele","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Werner","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Ahrens","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hoppe","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Marschke","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Staedt","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Hiort","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University of Luebeck, 23538 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613172649000_R1","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1210\/er.2000-0026","article-title":"Insights into G protein structure, function and regulation.","volume":"24","author":"Cabrera-Vera","year":"2003","journal-title":"Endocr Rev"},{"key":"2020071613172649000_R2","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1210\/en.2004-0865","article-title":"GNAS: normal and abnormal functions.","volume":"145","author":"Weinstein","year":"2004","journal-title":"Endocrinology"},{"key":"2020071613172649000_R3","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1073\/pnas.85.7.2081","volume":"85","author":"Kozasa","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613172649000_R4","doi-asserted-by":"crossref","first-page":"8893","DOI":"10.1073\/pnas.83.23.8893","article-title":"Human cDNA clones for four species of G\u03b1s signal transduction protein.","volume":"83","author":"Bray","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613172649000_R5","doi-asserted-by":"crossref","first-page":"8458","DOI":"10.1016\/S0021-9258(19)38910-0","article-title":"Alternative promoter and 5\u2032exon generate a novel Gs\u03b1 mRNA.","volume":"265","author":"Ishikawa","year":"1990","journal-title":"J Biol Chem"},{"key":"2020071613172649000_R6","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/372804a0","article-title":"XL\u03b1s is a new type of G protein.","volume":"372","author":"Kehlenbach","year":"1994","journal-title":"Nature"},{"key":"2020071613172649000_R7","doi-asserted-by":"crossref","first-page":"11657","DOI":"10.1074\/jbc.272.17.11657","article-title":"Molecular cloning and characterisation of NESP55, a novel chromogranin-like precursor of a peptide with 5-HT 1b receptor antagonist activity.","volume":"272","author":"Ischia","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071613172649000_R8","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/hmg\/9.5.835","article-title":"An imprinted antisense transcript at the human GNAS1 locus.","volume":"9","author":"Hayard","year":"2000","journal-title":"Hum Mol Genet"},{"key":"2020071613172649000_R9","doi-asserted-by":"crossref","first-page":"9587","DOI":"10.1016\/S0021-9258(18)67553-2","article-title":"Molecular basis for two forms of the G protein that stimulates adenylate cyclase.","volume":"261","author":"Robishaw","year":"1986","journal-title":"J Biol Chem"},{"key":"2020071613172649000_R10","doi-asserted-by":"crossref","first-page":"11375","DOI":"10.1016\/S0021-9258(18)60970-6","article-title":"Expression of cDNAs for G proteins in Escherichia coli. 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