{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:44:38Z","timestamp":1791092678356,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T00:00:00Z","timestamp":1693526400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["gimjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Genetics in Medicine"],"published-print":{"date-parts":[[2023,9]]},"DOI":"10.1016\/j.gim.2023.100883","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T17:17:31Z","timestamp":1683307051000},"page":"100883","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance"],"prefix":"10.1016","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-3765","authenticated-orcid":false,"given":"Rebecca S.","family":"Tooze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry A.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid M.A.","family":"Swagemakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Calpena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"McGowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Boute","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Collet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Laffargue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"de Leeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny V.","family":"Morton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Noons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte W.","family":"Ockeloen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Phipps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiong Yang","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Timberlake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemence","family":"Vanlerberghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Wall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.J.","family":"Mathijssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-049X","authenticated-orcid":false,"given":"Stephen R.F.","family":"Twigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-5481","authenticated-orcid":false,"given":"Andrew O.M.","family":"Wilkie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.gim.2023.100883_bib1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.jcms.2016.07.007","article-title":"Increase of prevalence of craniosynostosis","volume":"44","author":"Cornelissen","year":"2016","journal-title":"J\u00a0Craniomaxillofac Surg"},{"issue":"1","key":"10.1016\/j.gim.2023.100883_bib2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3171\/2020.1.PEDS2051","article-title":"Epidemiology of craniosynostosis in Norway","volume":"26","author":"T\u00f8nne","year":"2020","journal-title":"J\u00a0Neurosurg Pediatr"},{"issue":"3","key":"10.1016\/j.gim.2023.100883_bib3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ajhg.2015.07.006","article-title":"A\u00a0genetic-pathophysiological framework for craniosynostosis","volume":"97","author":"Twigg","year":"2015","journal-title":"Am J Hum Genet"},{"issue":"6","key":"10.1016\/j.gim.2023.100883_bib4","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1097\/MOP.0000000000000542","article-title":"Clinical genetics of craniosynostosis","volume":"29","author":"Wilkie","year":"2017","journal-title":"Curr Opin Pediatr"},{"issue":"1-2","key":"10.1016\/j.gim.2023.100883_bib5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000492266","article-title":"Genetic causes of craniosynostosis: an update","volume":"10","author":"Goos","year":"2019","journal-title":"Mol Syndromol"},{"key":"10.1016\/j.gim.2023.100883_bib6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1741-7007-5-47","article-title":"Classification and nomenclature of all human homeobox genes","volume":"5","author":"Holland","year":"2007","journal-title":"BMC Biol"},{"issue":"29","key":"10.1016\/j.gim.2023.100883_bib7","doi-asserted-by":"crossref","first-page":"26829","DOI":"10.1074\/jbc.M100239200","article-title":"The identification of Prx1 transcription regulatory domains provides a mechanism for unequal compensation by the Prx1 and Prx2 loci","volume":"276","author":"Norris","year":"2001","journal-title":"J\u00a0Biol Chem"},{"issue":"1","key":"10.1016\/j.gim.2023.100883_bib8","doi-asserted-by":"crossref","first-page":"4797","DOI":"10.1038\/s41467-021-24917-9","article-title":"The developing mouse coronal suture at single-cell resolution","volume":"12","author":"Farmer","year":"2021","journal-title":"Nat Commun"},{"issue":"2","key":"10.1016\/j.gim.2023.100883_bib9","first-page":"211","article-title":"Genetic analysis of Runx2 function during intramembranous ossification","volume":"143","author":"Takarada","year":"2016","journal-title":"Development"},{"issue":"5","key":"10.1016\/j.gim.2023.100883_bib10","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1002\/jcp.30728","article-title":"Post natal expression of Prx1 labels appendicular restricted progenitor cell populations of multiple tissues","volume":"237","author":"Bragdon","year":"2022","journal-title":"J\u00a0Cell Physiol"},{"issue":"4","key":"10.1016\/j.gim.2023.100883_bib11","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.stemcr.2017.03.002","article-title":"Postnatal calvarial skeletal stem cells expressing PRX1 reside exclusively in the calvarial sutures and are required for bone regeneration","volume":"8","author":"Wilk","year":"2017","journal-title":"Stem Cell Rep"},{"issue":"1","key":"10.1016\/j.gim.2023.100883_bib12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0925-4773(95)00389-I","article-title":"Expression patterns of the paired-related homeobox genes MHox\/Prxl and S8\/Prx2 suggest roles in development of the heart and the forebrain","volume":"52","author":"Leussink","year":"1995","journal-title":"Mech Dev"},{"issue":"1","key":"10.1016\/j.gim.2023.100883_bib13","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1006\/dbio.1998.9116","article-title":"Paired-related homeobox genes cooperate in Handplate and hindlimb zeugopod morphogenesis","volume":"205","author":"Lu","year":"1999","journal-title":"Dev Biol"},{"issue":"10","key":"10.1016\/j.gim.2023.100883_bib14","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1101\/gad.9.10.1237","article-title":"The paired-like homeo box gene MHox is required for early events of skeletogenesis in multiple lineages","volume":"9","author":"Martin","year":"1995","journal-title":"Genes Dev"},{"issue":"19","key":"10.1016\/j.gim.2023.100883_bib15","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1242\/dev.125.19.3831","article-title":"Prx1 and Prx2 in skeletogenesis: roles in the craniofacial region, inner ear and limbs","volume":"125","author":"ten Berge","year":"1998","journal-title":"Development"},{"issue":"3","key":"10.1016\/j.gim.2023.100883_bib16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/j.1399-0004.2010.01531.x","article-title":"PRRX1 is mutated in a fetus with agnathia-otocephaly","volume":"79","author":"Sergi","year":"2011","journal-title":"Clin Genet"},{"issue":"3","key":"10.1016\/j.gim.2023.100883_bib17","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1399-0004.2011.01730.x","article-title":"PRRX1 is mutated in an otocephalic newborn infant conceived by consanguineous parents","volume":"81","author":"\u00c7elik","year":"2012","journal-title":"Clin Genet"},{"issue":"4","key":"10.1016\/j.gim.2023.100883_bib18","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/ajmg.a.35879","article-title":"Recurrent agnathia-otocephaly caused by DNA replication slippage in PRRX1","volume":"161A","author":"Dasouki","year":"2013","journal-title":"Am J Med Genet A"},{"issue":"9","key":"10.1016\/j.gim.2023.100883_bib19","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/pd.3910","article-title":"Prenatal diagnosis and identification of heterozygous frameshift mutation in PRRX1 in an infant with agnathia-otocephaly","volume":"32","author":"Donnelly","year":"2012","journal-title":"Prenat Diagn"},{"issue":"1","key":"10.1016\/j.gim.2023.100883_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.107871","article-title":"Integrated transcriptome and network analysis reveals spatiotemporal dynamics of calvarial suturogenesis","volume":"32","author":"Holmes","year":"2020","journal-title":"Cell Rep"},{"issue":"5961","key":"10.1016\/j.gim.2023.100883_bib21","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.1181498","article-title":"Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays","volume":"327","author":"Drmanac","year":"2010","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.gim.2023.100883_bib22","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.ajhg.2018.04.014","article-title":"De novo and inherited loss-of-function variants in TLK2: clinical and genotype-phenotype evaluation of a distinct neurodevelopmental disorder","volume":"102","author":"Reijnders","year":"2018","journal-title":"Am J Hum Genet"},{"issue":"4","key":"10.1016\/j.gim.2023.100883_bib23","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ajhg.2019.02.006","article-title":"De novo missense substitutions in the gene encoding CDK8, a regulator of the mediator complex, cause a syndromic developmental disorder","volume":"104","author":"Calpena","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"35","key":"10.1016\/j.gim.2023.100883_bib24","doi-asserted-by":"crossref","first-page":"E7341","DOI":"10.1073\/pnas.1709255114","article-title":"De novo mutations in inhibitors of Wnt, BMP, and Ras\/ERK signaling pathways in non-syndromic midline craniosynostosis","volume":"114","author":"Timberlake","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"24","key":"10.1016\/j.gim.2023.100883_bib25","doi-asserted-by":"crossref","first-page":"5349","DOI":"10.1093\/bioinformatics\/btz582","article-title":"Amplimap: a versatile tool to process and analyze targeted NGS data","volume":"35","author":"Koelling","year":"2019","journal-title":"Bioinformatics"},{"issue":"7809","key":"10.1016\/j.gim.2023.100883_bib26","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.gim.2023.100883_bib27","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1038\/s41436-020-0817-2","article-title":"SMAD6 variants in craniosynostosis: genotype and phenotype evaluation","volume":"22","author":"Calpena","year":"2020","journal-title":"Genet Med"},{"issue":"14","key":"10.1016\/j.gim.2023.100883_bib28","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1242\/jcs.01152","article-title":"Impairment of SHOX nuclear localization as a cause for Leri-Weill syndrome","volume":"117","author":"Sabherwal","year":"2004","journal-title":"J\u00a0Cell Sci"},{"issue":"1","key":"10.1016\/j.gim.2023.100883_bib29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/humu.20187","article-title":"Alteration of DNA binding, dimerization, and nuclear translocation of SHOX homeodomain mutations identified in idiopathic short stature and Leri-Weill dyschondrosteosis","volume":"26","author":"Schneider","year":"2005","journal-title":"Hum Mutat"},{"issue":"9","key":"10.1016\/j.gim.2023.100883_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.xgen.2022.100168","article-title":"Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes","volume":"2","author":"Karczewski","year":"2022","journal-title":"Cell Genomics"},{"issue":"6","key":"10.1016\/j.gim.2023.100883_bib31","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ajmg.a.34049","article-title":"Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25","volume":"155A","author":"Burkardt","year":"2011","journal-title":"Am J Med Genet A"},{"issue":"12","key":"10.1016\/j.gim.2023.100883_bib32","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1002\/ajmg.a.37336","article-title":"Two further patients with the 1q24 deletion syndrome expand the phenotype: a possible role for the miR199-214 cluster in the skeletal features of the condition","volume":"167A","author":"Ashraf","year":"2015","journal-title":"Am J Med Genet A"},{"issue":"5","key":"10.1016\/j.gim.2023.100883_bib33","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1002\/ajmg.a.36856","article-title":"Refinement of genotype-phenotype correlation in 18 patients carrying a 1q24q25 deletion","volume":"167A","author":"Chatron","year":"2015","journal-title":"Am J Med Genet A"},{"issue":"W1","key":"10.1016\/j.gim.2023.100883_bib34","doi-asserted-by":"crossref","first-page":"W535","DOI":"10.1093\/nar\/gkab354","article-title":"PredictProtein \u2013 predicting protein structure and function for 29 years","volume":"49","author":"Bernhofer","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"10.1016\/j.gim.2023.100883_bib35","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.bbrc.2006.12.100","article-title":"An intact homeobox domain is required for complete nuclear localization of human Nanog","volume":"353","author":"Do","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"issue":"10","key":"10.1016\/j.gim.2023.100883_bib36","first-page":"4900","article-title":"Paired-like homeodomain 2B contributes to tumour progression and anti-autophagy in human lung cancer","volume":"11","author":"Wang","year":"2021","journal-title":"Am J Cancer Res"},{"issue":"7","key":"10.1016\/j.gim.2023.100883_bib37","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.cell.2008.05.023","article-title":"Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites","volume":"133","author":"Noyes","year":"2008","journal-title":"Cell"},{"issue":"23","key":"10.1016\/j.gim.2023.100883_bib38","doi-asserted-by":"crossref","first-page":"8931","DOI":"10.1073\/pnas.1200874109","article-title":"Structural basis for homeodomain recognition by the cell-cycle regulator geminin","volume":"109","author":"Zhou","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"10.1016\/j.gim.2023.100883_bib39","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1097\/00001756-199807130-00029","article-title":"Functional role of position 22 in the homeodomain of Brn-3 transcription factors","volume":"9","author":"Dawson","year":"1998","journal-title":"Neuroreport"},{"issue":"2","key":"10.1016\/j.gim.2023.100883_bib40","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/ajmg.a.33246","article-title":"Fetal constraint as a potential risk factor for craniosynostosis","volume":"152a","author":"Sanchez-Lara","year":"2011","journal-title":"Am J Med Genet A"},{"issue":"3","key":"10.1016\/j.gim.2023.100883_bib41","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.gde.2013.02.015","article-title":"New insights into the genetic basis of TAR (thrombocytopenia-absent radii) syndrome","volume":"23","author":"Albers","year":"2013","journal-title":"Curr Opin Genet Dev"},{"key":"10.1016\/j.gim.2023.100883_bib42","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.bone.2013.10.016","article-title":"Prx1 and 3.2kb Col1a1 promoters target distinct bone cell populations in transgenic mice","volume":"58","author":"Ouyang","year":"2014","journal-title":"Bone"},{"issue":"3","key":"10.1016\/j.gim.2023.100883_bib43","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/0092-8674(93)90379-5","article-title":"A\u00a0mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis","volume":"75","author":"Jabs","year":"1993","journal-title":"Cell"},{"key":"10.1016\/j.gim.2023.100883_bib44","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.20125","article-title":"Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles","volume":"5","author":"Timberlake","year":"2016","journal-title":"Elife"},{"issue":"20","key":"10.1016\/j.gim.2023.100883_bib45","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.1242\/dev.01390","article-title":"A\u00a0phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos","volume":"131","author":"Brugger","year":"2004","journal-title":"Development"},{"issue":"2","key":"10.1016\/j.gim.2023.100883_bib46","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ydbio.2005.04.019","article-title":"Threshold-specific requirements for Bmp4 in mandibular development","volume":"283","author":"Liu","year":"2005","journal-title":"Dev Biol"}],"container-title":["Genetics in Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1098360023008961?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1098360023008961?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T07:18:15Z","timestamp":1730963895000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1098360023008961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["S1098360023008961"],"URL":"https:\/\/doi.org\/10.1016\/j.gim.2023.100883","relation":{},"ISSN":["1098-3600"],"issn-type":[{"value":"1098-3600","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance","name":"articletitle","label":"Article Title"},{"value":"Genetics in Medicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.gim.2023.100883","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.","name":"copyright","label":"Copyright"}],"article-number":"100883"}}