{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:54:21Z","timestamp":1753883661980,"version":"3.41.2"},"reference-count":9,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Barts Health NHS Trust and Barts Charity","award":["MGU0550","G-001855"],"award-info":[{"award-number":["MGU0550","G-001855"]}]},{"name":"British Society of Paediatric Endocrinology and Diabetes"},{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","award":["MGU0458","G-002162"],"award-info":[{"award-number":["MGU0458","G-002162"]}],"id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["G0802796","BB\/W018276\/1"],"award-info":[{"award-number":["G0802796","BB\/W018276\/1"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collaborative Awards in Science and Engineering Studentship","award":["MR\/R015686\/2442100"],"award-info":[{"award-number":["MR\/R015686\/2442100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>GNAS variants were recently described in 1% of patients not known to have pseudohypoparathyroidism\/inactivating PTH\/PTHrP signalling disorder 2 in the UK Genetics of Obesity Study. We describe a new missense GNAS variant, c.791A &amp;gt; C, p.(Asp264Thr), in a family with obesity, hyperphagia and mild PTH resistance. A 6-year-old female (body mass index +4.3 SD score [SDS], height +1.9 SDS) presented with hyperphagia and obesity from age 3 years. She had subtle brachydactyly, macrocephaly, and mildly delayed development. The 12-year-old brother (height +2.1 SDS, body mass index +2.9 SDS) had hyperphagia, obesity, mildly delayed development, and autism. He had subtle brachydactyly, as did the affected mother. We assessed the functional effect of the mutant, measuring cAMP production in cells transfected with wild type and mutant GNAS after ligand stimulation. Cells with the mutant GNAS showed impaired cAMP generation through melanocortin receptor 4, GH releasing hormone receptor, and PTH receptor. These cases demonstrate the clinical heterogeneity of monogenic disease, suggesting a need to test for PHP1A in children with obesity even without classical signs of PHP1A.<\/jats:p>","DOI":"10.1210\/jcemcr\/luae125","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T07:09:06Z","timestamp":1722841746000},"source":"Crossref","is-referenced-by-count":0,"title":["A Novel Maternally Inherited <i>GNAS<\/i> Variant in a Family With Hyperphagia and Obesity: 3 Cases"],"prefix":"10.1210","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1549-427X","authenticated-orcid":false,"given":"Anand","family":"Ramakrishnan","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology, Barts Health NHS Trust\u2014Royal London Children's Hospital , Whitechapel Road, London E1 1FR , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-3171","authenticated-orcid":false,"given":"Dillon","family":"Popat","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, EC1M 6BQ, London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preetha","family":"Purushothaman","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology, Barts Health NHS Trust\u2014Royal London Children's Hospital , Whitechapel Road, London E1 1FR , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5146-8242","authenticated-orcid":false,"given":"Li F","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology, Barts Health NHS Trust\u2014Royal London Children's Hospital , Whitechapel Road, London E1 1FR , UK"},{"name":"Centre for Endocrinology, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, EC1M 6BQ, London , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-4126","authenticated-orcid":false,"given":"Evelien F","family":"Gevers","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology, Barts Health NHS Trust\u2014Royal London Children's Hospital , Whitechapel Road, London E1 1FR , UK"},{"name":"Centre for Endocrinology, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London , Charterhouse Square, EC1M 6BQ, London , 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height, body mass index and head circumference fitted by maximum penalized likelihood","volume":"17","author":"Cole","year":"1998","journal-title":"Stat Med"},{"issue":"5","key":"2024081401415751200_luae125-B4","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/0092-8674(92)90034-A","article-title":"Identification of effector-activating residues of Gs\u03b1","volume":"68","author":"Berlot","year":"1992","journal-title":"Cell"},{"issue":"8","key":"2024081401415751200_luae125-B5","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1038\/ijo.2012.200","article-title":"Energy expenditure in obese children with pseudohypoparathyroidism type 1a","volume":"37","author":"Shoemaker","year":"2013","journal-title":"Int J Obes"},{"issue":"6","key":"2024081401415751200_luae125-B6","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cmet.2009.05.004","article-title":"Central nervous system imprinting of the G protein gs\u03b1 and its role in metabolic 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