{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:43:14Z","timestamp":1790419394978,"version":"4.1.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016685","name":"Baylor-Hopkins Center for Mendelian Genomics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016685","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1 HG006542"],"award-info":[{"award-number":["UM1 HG006542"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medical Genetics"],"published-print":{"date-parts":[[2022,1]]},"DOI":"10.1016\/j.ejmg.2021.104377","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T18:33:06Z","timestamp":1636137186000},"page":"104377","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Expansion of the phenotypic and mutational spectrum of Carpenter syndrome"],"prefix":"10.1016","volume":"65","author":[{"given":"Rabab","family":"Khairat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha","family":"Elhossini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nara","family":"Sobreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Otaify","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal M.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab R.","family":"Abdel Raouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inas","family":"Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Aglan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia A.","family":"Temtamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"19","key":"10.1016\/j.ejmg.2021.104377_bib1","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1016\/j.cub.2019.07.090","article-title":"Planar cell polarity effector proteins inturned and fuzzy form a Rab23 GEF complex","volume":"29","author":"Gerondopoulos","year":"2019","journal-title":"Curr. Biol.: CB"},{"issue":"6","key":"10.1016\/j.ejmg.2021.104377_bib2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1399-0004.1997.tb02501.x","article-title":"A case of Carpenter syndrome diagnosed in a 20-week-old fetus with postmortem examination","volume":"51","author":"Balci","year":"1997","journal-title":"Clin. Genet."},{"issue":"4","key":"10.1016\/j.ejmg.2021.104377_bib3","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/ajmg.a.33327","article-title":"RAB23 mutation in a large family from Comoros Islands with Carpenter syndrome","volume":"152A","author":"Alessandrix","year":"2010","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ejmg.2021.104377_bib4","first-page":"464","article-title":"The association of Carpenter syndrome and situsinversustotalis: first case report","volume":"31","author":"Altunhan","year":"2011","journal-title":"Turk.Klin. J. Med. Sci."},{"issue":"5","key":"10.1016\/j.ejmg.2021.104377_bib5","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1034\/j.1601-5215.2003.00046.x","article-title":"Association of schizophrenia and Carpenter syndrome","volume":"15","author":"Bersani","year":"2003","journal-title":"Acta Neuropsychiatr."},{"key":"10.1016\/j.ejmg.2021.104377_bib6","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1046\/j.0960-7439.2001.00295.x","article-title":"Oral findings in carpenter syndrome","volume":"11","author":"Blankenstein","year":"2001","journal-title":"Int. J. Paediatr. Dent."},{"key":"10.1016\/j.ejmg.2021.104377_bib7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3389\/fpsyt.2017.00069","article-title":"Autism spectrum disorders and schizophrenia spectrum disorders: excitation\/inhibition imbalance and developmental trajectories","volume":"8","author":"Canitano","year":"2017","journal-title":"Front. Psychiatr."},{"key":"10.1016\/j.ejmg.2021.104377_bib8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/003591570900201481","article-title":"Acrocephaly, with other congenital malformations-autopsy","volume":"2","author":"Carpenter","year":"1909","journal-title":"Proc. Roy. Soc. Med."},{"key":"10.1016\/j.ejmg.2021.104377_bib10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3389\/fpsyt.2019.00450","article-title":"Co-occurrence of autism spectrum disorder and achondroplasia","volume":"10","author":"Dy","year":"2019","journal-title":"Front. Psychiatr."},{"key":"10.1016\/j.ejmg.2021.104377_bib11","author":"Dynamut web server"},{"issue":"6843","key":"10.1016\/j.ejmg.2021.104377_bib12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/35084089","article-title":"Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway","volume":"412","author":"Eggenschwiler","year":"2001","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2005.09.022","article-title":"Mouse Rab23 regulates hedgehog signaling from smoothened to Gli proteins","volume":"290","author":"Eggenschwiler","year":"2006","journal-title":"Dev. Biol."},{"issue":"11","key":"10.1016\/j.ejmg.2021.104377_bib16","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1002\/ajmg.a.36726","article-title":"Prenatal findings in carpenter syndrome and a novel mutation in RAB23","volume":"164A","author":"Haye","year":"2014","journal-title":"Am. J. Med. Genet."},{"issue":"6","key":"10.1016\/j.ejmg.2021.104377_bib17","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1086\/518047","article-title":"O. RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity","volume":"80","author":"Jenkins","year":"2007","journal-title":"Am. J. Hum. Genet."},{"issue":"4","key":"10.1016\/j.ejmg.2021.104377_bib18","doi-asserted-by":"crossref","first-page":"E2069","DOI":"10.1002\/humu.21457","article-title":"Carpenter syndrome: extended RAB23 mutation spectrum and analysis of nonsense-mediated mRNA decay","volume":"32","author":"Jenkins","year":"2011","journal-title":"Hum. Mutat."},{"issue":"11","key":"10.1016\/j.ejmg.2021.104377_bib20","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: the human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s11689-019-9268-y","article-title":"Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk","volume":"11","author":"Kumar","year":"2019","journal-title":"J. Neurodev. Disord."},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3390\/molecules25010091","article-title":"The significance of halogen bonding in ligand-receptor interactions: the lesson learned from molecular dynamic simulations of the D4 receptor","volume":"25","author":"Kurczab","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejmg.2021.104377_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2569-8_1","article-title":"Rab family of GTPases","volume":"1298","author":"Li","year":"2015","journal-title":"Methods Mol. Biol."},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib27","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5223\/pghn.2020.23.1.89","article-title":"Factors associated with advanced bone age in overweight and obese children","volume":"23","author":"Oh","year":"2020","journal-title":"Pediatric gastroenterology, hepatology & nutrition"},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib29","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/pro.3774","article-title":"Prediction of impacts of mutations on protein structure and interactions: SDM, a statistical approach, and mCSM, using machine learning","volume":"29","author":"Pandurangan","year":"2020","journal-title":"Protein Sci.: a publication of the Protein Society"},{"issue":"Pt A","key":"10.1016\/j.ejmg.2021.104377_bib30","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neubiorev.2017.01.008","article-title":"Targeting sonic hedgehog signaling in neurological disorders","volume":"74","author":"Patel","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"issue":"Pt A","key":"10.1016\/j.ejmg.2021.104377_bib31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neubiorev.2017.01.008","article-title":"Targeting sonic hedgehog signaling in neurological disorders","volume":"74","author":"Patel","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.ejmg.2021.104377_bib32","series-title":"The Human Gene Mutation Database, at the Institute of Medical Genetics in Cardiff","author":"Professional","year":"2021"},{"issue":"2","key":"10.1016\/j.ejmg.2021.104377_bib34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/ajmg.1320470228","article-title":"Carpenter syndrome with normal intelligence: Brazilian girl born to consanguineous parents","volume":"47","author":"Richieri-Costa","year":"1993","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ejmg.2021.104377_bib35","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/ajmg.1320200307","article-title":"Carpenter syndrome: natural history and clinical spectrum","volume":"20","author":"Robinson","year":"1985","journal-title":"Am. J. Med. Genet."},{"issue":"W1","key":"10.1016\/j.ejmg.2021.104377_bib36","doi-asserted-by":"crossref","first-page":"W350","DOI":"10.1093\/nar\/gky300","article-title":"DynaMut: predicting the impact of mutations on protein conformation, flexibility and stability","volume":"46","author":"Rodrigues","year":"2018","journal-title":"Nucleic Acids Res."},{"issue":"Pt 2","key":"10.1016\/j.ejmg.2021.104377_bib37","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1107\/S2052520617003109","article-title":"Relationships between hydrogen bonds and halogen bonds in biological systems","volume":"73","author":"Rowe","year":"2017","journal-title":"Acta crystallographica Section B, Structural science, crystal engineering and materials"},{"issue":"4","key":"10.1016\/j.ejmg.2021.104377_bib38","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib39","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13256-019-2043-6","article-title":"Autistic symptoms in Greig cephalopolysyndactyly syndrome: a family case report","volume":"13","author":"Siracusano","year":"2019","journal-title":"J. Med. Case Rep."},{"key":"10.1016\/j.ejmg.2021.104377_bib41","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ijporl.2003.10.009","article-title":"The Carpenter syndrome phenotype","volume":"68","author":"Tarhan","year":"2004","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"issue":"1","key":"10.1016\/j.ejmg.2021.104377_bib42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0022-3476(66)80368-2","article-title":"A. Carpenter's syndrome: acrocephalopolysyndactyly. An autosomal recessive syndrome","volume":"69","author":"Temtamy","year":"1966","journal-title":"J. Pediatr."},{"issue":"2","key":"10.1016\/j.ejmg.2021.104377_bib43","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3390\/genes8020048","article-title":"Primary cilia as a possible link between left-right asymmetry and neurodevelopmental diseases","volume":"25","author":"Trulioff","year":"2017","journal-title":"Genes"},{"issue":"5","key":"10.1016\/j.ejmg.2021.104377_bib44","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.ajhg.2012.08.027","article-title":"Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization","volume":"91","author":"Twigg","year":"2012","journal-title":"Am. J. Hum. Genet."},{"issue":"3","key":"10.1016\/j.ejmg.2021.104377_bib45","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/ajmg.a.36362","article-title":"Prenatal diagnosis of Carpenter syndrome: looking beyond craniosynostosis and polysyndactyly","volume":"164A","author":"Victorine","year":"2014","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.ejmg.2021.104377_bib46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fcell.2018.00008","article-title":"Signaling through the primary cilium","volume":"6","author":"Wheway","year":"2018","journal-title":"Frontiers in cell and developmental biology"},{"issue":"1\u20132","key":"10.1016\/j.ejmg.2021.104377_bib47","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/BF01665112","article-title":"Carpenter syndrome with normal intelligence and precocious growth","volume":"57","author":"White","year":"1981","journal-title":"Acta Neurochir."},{"issue":"2","key":"10.1016\/j.ejmg.2021.104377_bib48","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/ijos.2015.14","article-title":"The Hedgehog signalling pathway in bone formation","volume":"7","author":"Yang","year":"2015","journal-title":"Int. J. Oral Sci."}],"container-title":["European Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1769721221002433?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1769721221002433?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:52:25Z","timestamp":1761709945000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1769721221002433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["S1769721221002433"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmg.2021.104377","relation":{},"ISSN":["1769-7212"],"issn-type":[{"value":"1769-7212","type":"print"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Expansion of the phenotypic and mutational spectrum of Carpenter syndrome","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medical Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmg.2021.104377","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104377"}}