{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T17:14:29Z","timestamp":1788023669392,"version":"build-2784847793"},"reference-count":14,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1997,8]]},"abstract":"<jats:p>The craniosynostosis syndromes are a heterogeneous group of sporadic, autosomal dominant disorders with significant clinical overlap. Recently, we described a large family with autosomal dominant craniosynostosis suggestive of Saethre-Chotzen syndrome, in which linkage to the Saethre-Chotzen syndrome loci on 7p had been excluded. We now report the presence of a mutation in the fibroblast growth factor receptor 3 (FGFR3) in this family. The mutation, P250R, had been previously reported in 10 patients with non-syndromic craniosynostosis. Variable expression of this mutation is evident especially in two additional members of this family, one of whom is severely affected with pancraniosynostosis. The family provides a further example of genetic heterogeneity and variable expression of the craniosynostosis syndromes and broadens the phenotypic spectrum associated with the FGFR3 mutation P250R. In addition, we found a polymorphism (F384L) in the transmembrane domain of FGFR3 which occurs with a frequency of 3% in the Turkish population but is uncommon among Germans.<\/jats:p>","DOI":"10.1136\/jmg.34.8.683","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"683-684","source":"Crossref","is-referenced-by-count":38,"title":["Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family."],"prefix":"10.1136","volume":"34","author":[{"given":"A","family":"Golla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Lichmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"von Gernet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Winterpacht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Fairley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Murken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Schuffenhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1997,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/hmg\/4.3.323","article-title":"Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome","volume":"4","author":"Schell, U.; Hehr, A.; Feldman, G.J.","year":"1995","unstructured":"Schell U, Hehr A, Feldman GJ, et al. Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome. Hum Mol Genet 1995;4:323-8.","journal-title":"Hum Mol Genet"},{"key":"ref_2","doi-asserted-by":"crossref","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, M.; Schell, U.; Hehr, A.","year":"1994","unstructured":"Muenke M, Schell U, Hehr A, et al. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet 1994;8:269-74.","journal-title":"Nat Genet"},{"key":"ref_3","first-page":"98","article-title":"Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2","volume-title":"Nat Genet","volume":"8","author":"Jabs, E.W.; Li, X.; Scott, A.F.","year":"1994","unstructured":"Jabs EW, Li X, Scott AF, et al. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet 1994;8:98-103."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/ng0994-98","article-title":"Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome","volume":"8","author":"Reardon, W.; Winter, R.M.; Rutland, P.; Pulleyn, L.J.; Jones, B.M.; Malcolm, S.","year":"1994","unstructured":"Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet 1994; 8:98-103.","journal-title":"Nat Genet"},{"key":"ref_5","doi-asserted-by":"crossref","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, A.O.M.; Slaney, S.F.; Oldridge, M.","year":"1995","unstructured":"Wilkie AOM, Slaney SF, Oldridge M, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet 1995;9:165-72.","journal-title":"Nat Genet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/ng0295-108","article-title":"Le Merrer M. FGFR2 mutations in Pfeiffer syndrome","volume":"9","author":"Lajeunie, E.; Ma, H.W.; Bonaventure, J.; Munnich, A.","year":"1995","unstructured":"Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M. FGFR2 mutations in Pfeiffer syndrome. Nat Genet 1995;9: 108.","journal-title":"Nat Genet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/ng0295-173","article-title":"Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes","volume":"9","author":"Rutland, P.; Pulleyn, U.; Reardon, W.","year":"1995","unstructured":"Rutland P, Pulleyn U, Reardon W, et al. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet 1995;9:173-6.","journal-title":"Nat Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/ng1096-174","article-title":"Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes","volume":"14","author":"Bellus, G.A.; Gaudenz, K.; Zackai, E.H.","year":"1996","unstructured":"Bellus GA, Gaudenz K, Zackai EH, et al. Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet 1996;14:174-6.","journal-title":"Nat Genet"},{"key":"ref_9","doi-asserted-by":"crossref","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, A.; Thompson, L.; Zhu, Y.Z.","year":"1994","unstructured":"Shiang A, Thompson L, Zhu YZ, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 1994;78:335-42.","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ng0795-357","article-title":"A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia","volume":"10","author":"Bellus, G.A.; McIntosh, I.; Smith, E.A.","year":"1995","unstructured":"Bellus GA, McIntosh I, Smith EA, et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet 1995; 10:357-9.","journal-title":"Nat Genet"},{"key":"ref_11","first-page":"321","article-title":"Thanatophoric dysplasia (types I and II) caused by distinct mutations in the fibroblast growth factor receptor 3","volume-title":"Nat Genet","volume":"9","author":"Tavormina, P.L.; Shiang, R.; Thompson, L.M.","year":"1995","unstructured":"Tavormina PL, Shiang R, Thompson LM, et al. Thanatophoric dysplasia (types I and II) caused by distinct mutations in the fibroblast growth factor receptor 3. Nat Genet 1995;9:321-8."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/ng1295-462","article-title":"EW Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans","volume":"11","author":"Meyers, G.A.; Orlow, S.J.; Munro, I.R.; Przylepa, K.A.; Jabs","year":"1995","unstructured":"Meyers GA, Orlow SJ, Munro IR, Przylepa KA, Jabs EW Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet 1995;11:462-4.","journal-title":"Nat Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/(SICI)1096-8628(19960503)63:1<177::AID-AJMG31>3.0.CO;2-J","article-title":"Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p","volume":"63","author":"von Gernet S; S, Schuffenhauer; A, Golla","year":"1996","unstructured":"von Gernet S, Schuffenhauer S, Golla A, et al. Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p. AmJ Med Genet 1996;63: 177-84.","journal-title":"AmJ Med Genet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul, S.F.; Gish, W.; Miller, W.; Myers, E.W.; Lipman, D.","year":"1990","unstructured":"Altschul SF, Gish W, Miller W, Myers EW, Lipman D. Basic local alignment search tool. JMol Biol 1990;215:403-10.","journal-title":"JMol Biol"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.34.8.683","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T16:51:21Z","timestamp":1760719881000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.34.8.683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8]]},"references-count":14,"journal-issue":{"issue":"8","published-online":{"date-parts":[[1997,8,1]]},"published-print":{"date-parts":[[1997,8]]}},"alternative-id":["10.1136\/jmg.34.8.683"],"URL":"https:\/\/doi.org\/10.1136\/jmg.34.8.683","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8]]}}}