{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:39:50Z","timestamp":1792442390555,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":2117,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T00:00:00Z","timestamp":1528329600000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Pseudohypoparathyroidism type 1A (PHP1A), pseudoPHP (PPHP), and PHP type 1B (PHP1B) are caused by maternal and paternal GNAS mutations and abnormal methylation at maternal GNAS promoter(s), respectively. Adult PHP1A patients are reportedly obese and short, whereas most PPHP patients are born small. In addition to parathyroid hormone (PTH) resistance, PHP1A and PHP1B patients may display early-onset obesity. Because early-onset and severe obesity and short stature are daily burdens for PHP1A patients, we aimed at improving knowledge on the contribution of the GNAS transcripts to fetal and postnatal growth and fat storage. Through an international collaboration, we collected growth and weight data from birth until adulthood for 306 PHP1A\/PPHP and 220 PHP1B patients. PHP1A\/PPHP patients were smaller at birth than healthy controls, especially PPHP (length Z-score: PHP1A \u20131.1\u2009\u00b1\u20091.8; PPHP \u20133.0\u2009\u00b1\u20091.5). Short stature is observed in 64% and 59% of adult PHP1A and PPHP patients. PHP1B patients displayed early postnatal overgrowth (height Z-score at 1 year: 2.2\u2009\u00b1\u20091.3 and 1.3\u2009\u00b1\u20091.5 in autosomal dominant and sporadic PHP1B) followed by a gradual decrease in growth velocity resulting in normal adult height (Z-score for both: \u20130.4\u2009\u00b1\u20091.1). Early-onset obesity characterizes GNAS alterations and is associated with significant overweight and obesity in adults (bodey mass index [BMI] Z-score: 1.4\u2009\u00b1\u20092.6, 2.1\u2009\u00b1\u20092.0, and 1.4\u2009\u00b1\u20091.9 in PPHP, PHP1A, and PHP1B, respectively), indicating that reduced Gs\u03b1 expression is a contributing factor. The growth impairment in PHP1A\/PPHP may be due to Gs\u03b1 haploinsufficiency in the growth plates; the paternal XL\u03b1s transcript likely contributes to prenatal growth; for all disease variants, a reduced pubertal growth spurt may be due to accelerated growth plate closure. Consequently, early diagnosis and close follow-up is needed in patients with GNAS defects to screen and intervene in case of early-onset obesity and decreased growth velocity. \u00a9 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3450","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T15:55:36Z","timestamp":1524671736000},"page":"1480-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Genetic and Epigenetic Defects at the GNAS Locus Lead to Distinct Patterns of Skeletal Growth but Similar Early-Onset Obesity"],"prefix":"10.1093","volume":"33","author":[{"given":"Patrick","family":"Hanna","sequence":"first","affiliation":[{"name":"INSERM U1169 and Paris Sud Paris-Saclay UniversityBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Grybek","sequence":"additional","affiliation":[{"name":"INSERM U1169 and Paris Sud Paris-Saclay UniversityBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiomar","family":"Perez de Nanclares","sequence":"additional","affiliation":[{"name":"Molecular (Epi)Genetics LaboratoryBioAraba National Health InstituteOSI Araba University HospitalVitoria-GasteizSpain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a C","family":"Tran","sequence":"additional","affiliation":[{"name":"Caen University HospitalMolecular Genetics LaboratoryUniversit\u00e9 Caen NormandieMedical SchoolBioTARGENCaen Normandy UniversityCaenFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"de Sanctis","sequence":"additional","affiliation":[{"name":"Paediatric Endocrinology Unit, Margherita Children Hospital, Department of Public Health and Pediatric Sciences, University of TorinoTorinoItaly"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Elli","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Endocrinology and Diabetology UnitDepartment of Clinical Sciences and Community HealthUniversity of MilanMilanItaly"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Errea","sequence":"additional","affiliation":[{"name":"Molecular (Epi)Genetics LaboratoryBioAraba National Health InstituteOSI Araba University HospitalVitoria-GasteizSpain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Francou","sequence":"additional","affiliation":[{"name":"APHP, Department of Molecular GeneticsBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kamenicky","sequence":"additional","affiliation":[{"name":"APHP, Reference Center for Rare Disorders of the Calcium and Phosphate MetabolismFiliere OSCAR and Platform of expertise for rare diseases Paris-SudBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"},{"name":"APHP, Department of Endocrinology and Reproductive DiseasesBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Linglart","sequence":"additional","affiliation":[{"name":"APHP, Reference Center for Rare Disorders of the Calcium and Phosphate MetabolismFiliere OSCAR and Platform of expertise for rare diseases Paris-SudBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arrate","family":"Pereda","sequence":"additional","affiliation":[{"name":"Molecular (Epi)Genetics LaboratoryBioAraba National Health InstituteOSI Araba University HospitalVitoria-GasteizSpain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya","family":"Rothenbuhler","sequence":"additional","affiliation":[{"name":"APHP, Endocrinology and Diabetes for ChildrenBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"},{"name":"APHP, Reference Center for Rare Disorders of the Calcium and Phosphate MetabolismFiliere OSCAR and Platform of expertise for rare diseases Paris-SudBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Tessaris","sequence":"additional","affiliation":[{"name":"Paediatric Endocrinology Unit, Margherita Children Hospital, Department of Public Health and Pediatric Sciences, University of TorinoTorinoItaly"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Thiele","sequence":"additional","affiliation":[{"name":"Division of Experimental Pediatric Endocrinology and Diabetes Department of PediatricsCenter of Brain, Behavior and MetabolismUniversity of L\u00fcbeckL\u00fcbeckGermany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Usardi","sequence":"additional","affiliation":[{"name":"APHP, Reference Center for Rare Disorders of the Calcium and Phosphate MetabolismFiliere OSCAR and Platform of expertise for rare diseases Paris-SudBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley H","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Kottler","sequence":"additional","affiliation":[{"name":"Caen University HospitalMolecular Genetics LaboratoryUniversit\u00e9 Caen NormandieMedical SchoolBioTARGENCaen Normandy UniversityCaenFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit and Pediatric Nephrology UnitMassachusetts General Hospital and Harvard Medical SchoolBostonMAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Endocrinology and Diabetology UnitDepartment of Clinical Sciences and Community HealthUniversity of MilanMilanItaly"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Linglart","sequence":"additional","affiliation":[{"name":"APHP, Endocrinology and Diabetes for ChildrenBic\u00eatre Paris Sud HospitalLe Kremlin Bic\u00eatreFrance"},{"name":"APHP, Reference Center for Rare Disorders of the Calcium and Phosphate MetabolismFiliere OSCAR and Platform of expertise for rare 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