{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:25:59Z","timestamp":1791206759761,"version":"4.1.0"},"reference-count":31,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:p>Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have previously been identified in Crouzon syndrome, an autosomal dominant condition involving premature fusion of the cranial sutures. Several different missense and other mutations have been identified in Crouzon syndrome patients, clustering around the third immunoglobulin-like domain. We report here the identification of a mutation in the transmembrane region of FGFR3, common to three unrelated patients with classical Crouzon syndrome and acanthosis nigricans, a dermatological condition associated with thickening and abnormal pigmentation of the skin. The mutation within the FGFR3 transcript was determined by direct sequencing as a specific gcg to gag transversion, resulting in an amino acid substitution ala391glu within the transmembrane region.<\/jats:p>","DOI":"10.1136\/jmg.33.9.744","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"744-748","source":"Crossref","is-referenced-by-count":79,"title":["A recurrent mutation, ala391glu, in the transmembrane region of FGFR3 causes Crouzon syndrome and acanthosis nigricans."],"prefix":"10.1136","volume":"33","author":[{"given":"D","family":"Wilkes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Rutland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L J","family":"Pulleyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Reardon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J P","family":"Ellis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R M","family":"Winter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Malcolm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,9,1]]},"reference":[{"key":"ref_1","article-title":"Craniosynostosis: diagnosis, evaluation and management","author":"MM, Jr, Cohen","year":"1986","unstructured":"Cohen MM Jr. Craniosynostosis: diagnosis, evaluation and management. New York: Raven, 1986."},{"key":"ref_2","article-title":"The London dysmorphology database","author":"Winter, R.M.; Baraitser, M.","year":"1994","unstructured":"Winter RM, Baraitser M. The London dysmorphology database. Oxford: Oxford University Press, 1994."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S1357-4310(95)90837-4","article-title":"The molecular pathology of syndromic craniosynostosis","volume":"11","author":"Reardon, W.; Winter, R.M.","year":"1995","unstructured":"Reardon W, Winter RM. The molecular pathology of syndromic craniosynostosis Mol Med Today 1995; 11:432-7.","journal-title":"Mol Med Today"},{"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, U.; Jones, B.M.; Malcolm, S.","year":"1994","unstructured":"Reardon W, Winter RM, Rutland P, Pulleyn U, Jones BM, Malcolm S. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nature Genet 1994;8:98-103.","journal-title":"Nature 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. Nature Genet 1995;9:165-72.","journal-title":"Nature Genet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ng1194-275","article-title":"Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2","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. Nature Genet 1994;8:275-84.","journal-title":"Nature Genet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng1194-269","article-title":"A commoni 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 commoni mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nature Genet 1994;8:269-73.","journal-title":"Nature Genet"},{"key":"ref_8","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, L.J.; Reardon, W.","year":"1995","unstructured":"Rutland P, Pulleyn LJ, Reardon W, et al. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nature Genet 1995;9:173-6.","journal-title":"Nature Genet"},{"key":"ref_9","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 Molec Genet 1995;4:323-8.","journal-title":"Hum Molec Genet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/ng0295-108","article-title":"FGFR2 mutations in Pfeiffer syndrome","volume":"9","author":"Lajeunie, E.; Ma, H.W.; Bonaventure, J.; Munnich, A.; Le Merrer, M.; Renier, D.","year":"1995","unstructured":"Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D. FGFR2 mutations in Pfeiffer syndrome. Nature Genet 1995;9:108.","journal-title":"Nature Genet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1093\/hmg\/4.7.1229","article-title":"Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability","volume":"4","author":"Park, W.; Meyers, G.A.; Li, X.","year":"1995","unstructured":"Park W, Meyers GA, Li X, et al. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Molec Genet 1995;4: 1229-33.","journal-title":"Hum Molec Genet"},{"key":"ref_12","article-title":"Fibroblast growth factor receptor 2","volume-title":"mutations in craniosynostosis. Proc NatlAcad Sci USA","author":"Malcolm, S.; Reardon, W.","unstructured":"Malcolm S, Reardon W Fibroblast growth factor receptor 2 mutations in craniosynostosis. Proc NatlAcad Sci USA (in press)."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1093\/hmg\/4.8.1387","article-title":"Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common point mutation shared with Jackson-Weiss syndrome","volume":"4","author":"Gorry, M.G.; Preston, R.A.; White, G.J.","year":"1995","unstructured":"Gorry MG, Preston RA, White GJ, et al. Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common point mutation shared with Jackson-Weiss syndrome. Hum Molec Genet 1995;4:1387-90.","journal-title":"Hum Molec Genet"},{"key":"ref_14","doi-asserted-by":"crossref","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, M.; Wilkie, A.O.M.; Slaney, S.F.","year":"1995","unstructured":"Oldridge M, Wilkie AOM, Slaney SF, et al. Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome. Hum Molec Genet 1995;4: 1077-82.","journal-title":"Hum Molec Genet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ng0395-232","article-title":"Effect on splicing of a silent FGFR2 mutation in Crouzon syndrome","volume":"9","author":"Li, X.; Park, W.; Pyeritz, R.E.; Jabs, E.W.","year":"1995","unstructured":"Li X, Park W, Pyeritz RE, Jabs EW. Effect on splicing of a silent FGFR2 mutation in Crouzon syndrome. Nature Genet 1995;9:232-3.","journal-title":"Nature Genet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ng0694-149","article-title":"A gene for Crouzon craniofacial dysostosis maps to the long arm of chromosome 10","volume":"7","author":"Preston, R.A.; Post, J.C.; Keats, B.J.B.","year":"1994","unstructured":"Preston RA, Post JC, Keats BJB, et al. A gene for Crouzon craniofacial dysostosis maps to the long arm of chromosome 10. Nature Genet 1994;7:149-53.","journal-title":"Nature Genet"},{"key":"ref_17","first-page":"418","article-title":"Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 1 Oq23-q26","volume-title":"Genomics","volume":"23","author":"Li, X.; Lewanda, A.F.; Eluma, F.","year":"1994","unstructured":"Li X, Lewanda AF, Eluma F, et al. Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 1 Oq23-q26. Genomics 1994;23:418-24."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1346-8138.1992.tb03193.x","article-title":"An association of acanthosis nigricans and Crouzon syndrome","volume":"19","author":"Koizumi, H.; Tomoyori, T.; Sato, K.C.; Ohkawara, A.","year":"1992","unstructured":"Koizumi H, Tomoyori T, Sato KC, Ohkawara A. An association of acanthosis nigricans and Crouzon syndrome. J Dermatol 1992;19:122-6.","journal-title":"J Dermatol"},{"key":"ref_19","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":"8","author":"Shiang, R.; Thompson, L.M.; Zhu, Y.Z.","year":"1994","unstructured":"Shiang R, Thompson LM, Zhu YZ, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 1994;8:335-42.","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","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, F.; Bonaventure, J.; Legeai-Mallet, L.","year":"1994","unstructured":"Rousseau F, Bonaventure J, Legeai-Mallet L, et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 1994;371:252-4.","journal-title":"Nature"},{"key":"ref_21","first-page":"368","article-title":"Achondroplasia is defined by recurrent G380R mutations of FGFR3","volume":"56","author":"Bellus, G.A.; Hefferon, T.W.; de Luna, R.I.O.","year":"1995","unstructured":"Bellus GA, Hefferon TW, de Luna RIO, et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. Am JtHum Genet 1995;56:368-73.","journal-title":"Am JtHum Genet"},{"key":"ref_22","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, A.E.","year":"1995","unstructured":"Bellus GA, McIntosh I, Smith AE, et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nature Genet 1995;10:357-9.","journal-title":"Nature Genet"},{"key":"ref_23","first-page":"47","article-title":"Hypochondroplasia: a second mutation of fibroblast growth factor receptor 3 (FGFR3) at nucleotide 1620","volume":"57","author":"Bellus, G.A.; Sazabo, J.K.; McIntosh, L.","year":"1955","unstructured":"Bellus GA, Sazabo JK, McIntosh L, et al.Hypochondroplasia: a second mutation of fibroblast growth factor receptor 3 (FGFR3) at nucleotide 1620. Am J Hum Genet 1955;57:A47.","journal-title":"Am J Hum Genet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/ng0395-321","article-title":"Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3","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 fibroblast growth factor receptor 3. Nature Genet 1995;9:321-30.","journal-title":"Nature Genet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1093\/hmg\/4.11.2175","article-title":"Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type","volume":"4","author":"Tavormina, P.L.; Rimoin, D.L.; Cohn, D.H.; Zhu, Y.; Shiang, R.; Wasmuth, J.J.","year":"1995","unstructured":"Tavormina PL, Rimoin DL, Cohn DH, Zhu Y, Shiang R, Wasmuth JJ. Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I. Hum Molec Genet 1995;4:2175-7.","journal-title":"I. Hum Molec Genet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/ng0595-11","article-title":"Stop codon FGFR3 mutations in thanatophoric dwarfism type","volume":"10","author":"Rousseau, F.; Saugieer, P.; LeMerrer, M.","year":"1995","unstructured":"Rousseau F, Saugieer P, LeMerrer M, et al. Stop codon FGFR3 mutations in thanatophoric dwarfism type I. Nature Genet 1995; 10: 11-12.","journal-title":"I. Nature Genet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller, S.A.; Dykes, D.D.; Polesky, H.F.","year":"1988","unstructured":"Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.","journal-title":"Nucleic Acids Res"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1365-2141.1991.tb08016.x","article-title":"A simple and rapid method of direct sequencing using Dynabeads","volume":"79","author":"Thein, S.L.; Hinton, J.","year":"1991","unstructured":"Thein SL, Hinton J. A simple and rapid method of direct sequencing using Dynabeads. Br Haematol 1991;79: 113-15.","journal-title":"Br Haematol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/ng1295-462","article-title":"Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans","volume":"11","author":"Myers, G.A.; Orlow, S.J.; Munro, I.R.; Prylepa, A.; Jabs, E.W.","year":"1995","unstructured":"Myers GA, Orlow SJ, Munro IR, Prylepa A, Jabs EW. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nature Genet 1995;11:462-4.","journal-title":"Nature Genet"},{"key":"ref_30","first-page":"423","article-title":"Unique expression pattern of FGF receptor 3 gene during mouse organogenisis","volume":"155","author":"Peters, K.; Ornitz, D.M.; Werner, S.; Williams, L.","year":"1995","unstructured":"Peters K, Ornitz DM, Werner S, Williams L. Unique expression pattern of FGF receptor 3 gene during mouse organogenisis. Dev Biol 1995;155:423-30.","journal-title":"Dev Biol"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0092-8674(95)90112-4","article-title":"Regulation of growth factor activation by proteoglycans: what is the role of low affinity receptors","volume":"83","author":"Schlessinger, J.; Lax, I.; Lemmon, M.","year":"1995","unstructured":"Schlessinger J, Lax I, Lemmon M. Regulation of growth factor activation by proteoglycans: what is the role of low affinity receptors. Cell 1995;83:357-60.","journal-title":"Cell"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.33.9.744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T06:29:09Z","timestamp":1760768949000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.33.9.744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,9]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[1996,9,1]]},"published-print":{"date-parts":[[1996,9]]}},"alternative-id":["10.1136\/jmg.33.9.744"],"URL":"https:\/\/doi.org\/10.1136\/jmg.33.9.744","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,9]]}}}