{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:55:35Z","timestamp":1790434535848,"version":"4.1.0"},"reference-count":18,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,3]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> Apert's syndrome is characterized by faciocraniosynostosis and severe bony and cutaneous syndactyly of all four limbs. The molecular basis for this syndrome appears remarkably specific: two adjacent amino acid substitutions (either S252W or P253R) occurring in the linking region between the second and third immunoglobulin domains of the <jats:italic>fibroblast growth factor receptor (FGFR)2<\/jats:italic> gene. The goal of this study was to examine the phenotype\/genotype correlations in patients with Apert's syndrome.<\/jats:p><jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> In the present study, 36 patients with Apert's syndrome were screened for genetic mutations. Mutations were detected in all cases. In one of the patients there was a rare mutation consisting of a double\u2014base pair substitution in the same codon (S252F). A phenotypical survey of our cases was performed and showed the clinical variability of this syndrome. In two patients there was no clinical or radiological evidence of craniosynostosis. In two other patients with atypical forms of syndactyly and cranial abnormalities, the detection of a specific mutation was helpful in making the diagnosis.<\/jats:p><jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> The P253R mutation appears to be associated with the more severe forms, with regard to the forms of syndactyly and to mental outcome. The fact that mutations found in patients with Apert's syndrome are usually confined to a specific region of the <jats:italic>FGFR2<\/jats:italic> exon IIIa may be useful in making the diagnosis and allowing genetic counseling in difficult cases.<\/jats:p>","DOI":"10.3171\/jns.1999.90.3.0443","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:21:37Z","timestamp":1242235297000},"page":"443-447","source":"Crossref","is-referenced-by-count":108,"title":["Clinical variability in patients with Apert's syndrome"],"prefix":"10.3171","volume":"90","author":[{"given":"Elisabeth","family":"Lajeunie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoda","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"El Ghouzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"de Parseval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Journeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Gonzales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Lise","family":"Delezoide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacky","family":"Bonaventure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Le Merrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Renier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Bull Mem Soc Med Hop","first-page":"1310","article-title":"De l'acroc\u00e9phalosyndactylie.","volume":"243","author":"Apert","year":"1906"},{"key":"b2","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/ng0795-357","article-title":"A recurrent mutation in the tyrosine kinase domain of the fibroblast growth factor receptor 3 causes hypochondroplasia.","volume":"10","author":"Bellus","year":"1995"},{"key":"b3","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3171\/jns.1995.83.4.0575","article-title":"Chronic tonsillar herniation in Crouzon's and Apert's syndromes: the role of the premature synostosis of the lambdoid suture.","volume":"83","author":"Cinalli","year":"1995"},{"key":"b4","series-title":"Am J Med Genet","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/ajmg.1320570119","article-title":"Hands and feet in the Apert syndrome.","volume":"57","author":"Cohen","year":"1995"},{"key":"b5","series-title":"Am J Med Genet","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1002\/ajmg.1320420505","article-title":"Birth prevalence study of the Apert syndrome.","volume":"42","author":"Cohen","year":"1992"},{"key":"b6","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/ng0295-108","article-title":"FGFR2 mutations in Pfeiffer syndrome.","volume":"9","author":"Lajeunie","year":"1995"},{"key":"b7","series-title":"Am J Hum Genet","first-page":"491","article-title":"FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and Pfeiffer syndromes: evidence for missense changes, insertions, and a deletion due to alternative RNA splicing.","volume":"58","author":"Meyers","year":"1996"},{"key":"b8","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/ng0596-48","article-title":"Exclusive paternal origin of new mutations in Apert syndrome.","volume":"13","author":"Moloney","year":"1996"},{"key":"b9","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/ng1194-269","article-title":"A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome.","volume":"8","author":"Muenke","year":"1994"},{"key":"b10","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/hmg\/6.1.137","article-title":"Genotype-phenotype correlation for nucleotide substitution in the IgII-IgIII linker of FGFR2.","volume":"6","author":"Oldridge","year":"1997"},{"key":"b11","series-title":"Hum Mol Genet","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1093\/hmg\/4.6.1077","article-title":"Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome.","volume":"4","author":"Oldridge","year":"1995"},{"key":"b12","series-title":"Development","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1242\/dev.113.4.1419","article-title":"Developmental expression of two murine fibroblast growth factor receptors, flg and bek.","volume":"113","author":"Orr-Urtreger","year":"1991"},{"key":"b13","series-title":"Am J Hum Genet","first-page":"321","article-title":"Analysis of phenotypic features and mutations in Apert syndrome.","volume":"57","author":"Park","year":"1995"},{"key":"b14","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3171\/jns.1996.85.1.0066","article-title":"Prognosis for mental function in Apert's syndrome.","volume":"85","author":"Renier","year":"1996"},{"key":"b15","series-title":"Nature","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/371252a0","article-title":"Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.","volume":"371","author":"Rousseau","year":"1994"},{"key":"b16","series-title":"Cell","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/0092-8674(94)90302-6","article-title":"Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.","volume":"78","author":"Shiang","year":"1994"},{"key":"b17","series-title":"Am J Hum Genet","first-page":"923","article-title":"Differential effects of FGFR2 mutations on syndactyly and cleft palate in Apert syndrome.","volume":"58","author":"Slaney","year":"1996"},{"key":"b18","series-title":"Nat Genet","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/ng0295-165","article-title":"Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome.","volume":"9","author":"Wilkie","year":"1995"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/90\/3\/article-p443.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/90\/3\/article-p443.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/90\/3\/article-p443.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,13]],"date-time":"2022-11-13T02:46:00Z","timestamp":1668307560000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/90\/3\/article-p443.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3]]},"references-count":18,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.3171\/jns.1999.90.3.0443","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[1999,3]]}}}