{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:55:05Z","timestamp":1792695305811,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Apert syndrome is a recognizable craniofacial condition characterized by craniosynostosis, hypertelorism, exorbitism, midface hypoplasia, and complex symmetrical bony and cutaneous \u2018mitten\u2019 syndactyly of all four limbs. Around 98% of affected patients have one of two heterozygous missense variants in the\n                    <jats:italic>FGFR2<\/jats:italic>\n                    gene, encoding either p.(Ser252Trp) (S252W) or p.(Pro253Arg) (P253R). We report a patient with unicoronal craniosynostosis and near normal limbs, in whom we unexpectedly identified a heterozygous\n                    <jats:italic>FGFR2<\/jats:italic>\n                    S252W variant. Her mother, who had no history suggestive of craniosynostosis and only mild brachydactyly, was also found to carry the variant. We discuss evidence that the presence of a second novel\n                    <jats:italic>FGFR2<\/jats:italic>\n                    p.(Gly261Arg) missense variant, identified in\n                    <jats:italic>cis<\/jats:italic>\n                    in both patients, could explain the mild phenotype. A similar mechanism may be responsible for occasional reports of Pfeiffer syndrome associated with a common Apert genotype, for which no molecular mechanism has been elucidated previously. Our findings provide further insight into the mechanism of the severe syndactyly that is usually characteristic of Apert syndrome.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64221","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:23:28Z","timestamp":1755858208000},"page":"215-222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Absence of Syndactyly Associated With the Common Apert\n                    <scp>FGFR2 S252W<\/scp>\n                    Mutation: A Clinical Report and Likely Molecular Explanation"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3985-0697","authenticated-orcid":false,"given":"Ramy","family":"Saad","sequence":"first","affiliation":[{"name":"Clinical Genetics, North East Thames Regional Genetics Service Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"},{"name":"Genetics and Genomic Medicine UCL Great Ormond Street Institute of Child Health  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Lawn","sequence":"additional","affiliation":[{"name":"Molecular Genetics North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honor","family":"Gartland","sequence":"additional","affiliation":[{"name":"Molecular Genetics North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Steel","sequence":"additional","affiliation":[{"name":"Molecular Genetics North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Barns\u2010Jenkins","sequence":"additional","affiliation":[{"name":"Molecular Genetics North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"James","sequence":"additional","affiliation":[{"name":"Craniofacial Service Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Hay","sequence":"additional","affiliation":[{"name":"Clinical Genetics, North East Thames Regional Genetics Service Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"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":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1200-2858","authenticated-orcid":false,"given":"Louise C.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Clinical Genetics, North East Thames Regional Genetics Service Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002560050203"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0911064"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320570119"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.MCR\u201008\u20100021"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010018\u20100071\u20106"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24649"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500267102"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21648"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37862"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121183798"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh235"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000048802"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.235"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.177956"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0596\u201048"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1194\u2010269"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.01.023"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/302245"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1549"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.8.677"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2003.09.040"},{"issue":"5","key":"e_1_2_12_23_1","first-page":"923","article-title":"Differential Effects of FGFR2 Mutations on Syndactyly and Cleft Palate in Apert Syndrome","volume":"58","author":"Slaney S. F.","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2014.09.005"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fsc.2023.07.002"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20101\u201019"},{"key":"e_1_2_12_27_1","volume-title":"GeneReviews","author":"Wenger T.","year":"1998"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0295\u2010165"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja202366"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.26.14536"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1112890"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64221","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.64221","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:53:54Z","timestamp":1792655634000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,22]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/ajmg.a.64221"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64221","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,22]]},"assertion":[{"value":"2025-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}