2fdb

Structural highlights

Disease

[FGF8_HUMAN] Defects in FGF8 are the cause of hypogonadotropic hypogonadism 6 with or without anosmia (HH6) [MIM:612702]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).^[1] [FGFR2_HUMAN] Defects in FGFR2 are the cause of Crouzon syndrome (CS) [MIM:123500]; also called craniofacial dysostosis type I (CFD1). CS is an autosomal dominant syndrome characterized by craniosynostosis (premature fusion of the skull sutures), hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular prognathism.^{[2] [3]} [:]^{[4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]} Defects in FGFR2 are a cause of Jackson-Weiss syndrome (JWS) [MIM:123150]. JWS is an autosomal dominant craniosynostosis syndrome characterized by craniofacial abnormalities and abnormality of the feet: broad great toes with medial deviation and tarsal-metatarsal coalescence.^{[20] [21] [22] [23] [24] [25]} Defects in FGFR2 are a cause of Apert syndrome (APRS) [MIM:101200]; also known as acrocephalosyndactyly type 1 (ACS1). APRS is a syndrome characterized by facio-cranio-synostosis, osseous and membranous syndactyly of the four extremities, and midface hypoplasia. The craniosynostosis is bicoronal and results in acrocephaly of brachysphenocephalic type. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations.^{[26] [27] [28] [29] [30] [31] [32] [33] [34]} Defects in FGFR2 are a cause of Pfeiffer syndrome (PS) [MIM:101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly. Three subtypes of Pfeiffer syndrome have been described: mild autosomal dominant form (type 1); cloverleaf skull, elbow ankylosis, early death, sporadic (type 2); craniosynostosis, early demise, sporadic (type 3).^{[35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48]} Defects in FGFR2 are the cause of Beare-Stevenson cutis gyrata syndrome (BSCGS) [MIM:123790]. BSCGS is an autosomal dominant condition is characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death.^{[49] [50] [51]} Defects in FGFR2 are the cause of familial scaphocephaly syndrome (FSPC) [MIM:609579]; also known as scaphocephaly with maxillary retrusion and mental retardation. FSPC is an autosomal dominant craniosynostosis syndrome characterized by scaphocephaly, macrocephaly, hypertelorism, maxillary retrusion, and mild intellectual disability. Scaphocephaly is the most common of the craniosynostosis conditions and is characterized by a long, narrow head. It is due to premature fusion of the sagittal suture or from external deformation.^{[52] [53] [54]} Defects in FGFR2 are a cause of lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]; also known as Levy-Hollister syndrome. LADDS is a form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. LADDS is an autosomal dominant syndrome characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed.^{[55] [56] [57]} Defects in FGFR2 are the cause of Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (ABS2) [MIM:207410]. A rare syndrome characterized by craniosynostosis, radiohumeral synostosis present from the perinatal period, midface hypoplasia, choanal stenosis or atresia, femoral bowing and multiple joint contractures. Arachnodactyly and/or camptodactyly have also been reported.^{[58] [59]} Defects in FGFR2 are the cause of Bent bone dysplasia syndrome (BBDS) [MIM:614592]. BBDS is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Dysmorphic facial features included low-set ears, hypertelorism, midface hypoplasia, prematurely erupted fetal teeth, and micrognathia.^{[60] [61]}

Function

[FGF8_HUMAN] Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryogenesis. Required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system.^{[62] [63] [64]} [FGFR2_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.^{[65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] [79]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Fibroblast growth factor 3D structures
• Fibroblast growth factor receptor 3D receptor

References

1. ↑ Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y, Jacobson-Dickman EE, Eliseenkova AV, Ma J, Dwyer A, Quinton R, Na S, Hall JE, Huot C, Alois N, Pearce SH, Cole LW, Hughes V, Mohammadi M, Tsai P, Pitteloud N. Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest. 2008 Aug;118(8):2822-31. doi: 10.1172/JCI34538. PMID:18596921 doi:10.1172/JCI34538
2. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
3. ↑ Chen H, Ma J, Li W, Eliseenkova AV, Xu C, Neubert TA, Miller WT, Mohammadi M. A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. Mol Cell. 2007 Sep 7;27(5):717-30. PMID:17803937 doi:http://dx.doi.org/10.1016/j.molcel.2007.06.028
4. ↑ Gorry MC, Preston RA, White GJ, Zhang Y, Singhal VK, Losken HW, Parker MG, Nwokoro NA, Post JC, Ehrlich GD. Crouzon syndrome: mutations in two spliceoforms of FGFR2 and a common point mutation shared with Jackson-Weiss syndrome. Hum Mol Genet. 1995 Aug;4(8):1387-90. PMID:7581378
5. ↑ 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 Sep;8(1):98-103. PMID:7987400 doi:http://dx.doi.org/10.1038/ng0994-98
6. ↑ Jabs EW, Li X, Scott AF, Meyers G, Chen W, Eccles M, Mao JI, Charnas LR, Jackson CE, Jaye M. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet. 1994 Nov;8(3):275-9. PMID:7874170 doi:http://dx.doi.org/10.1038/ng1194-275
7. ↑ Oldridge M, Wilkie AO, Slaney SF, Poole MD, Pulleyn LJ, Rutland P, Hockley AD, Wake MJ, Goldin JH, Winter RM, et al.. Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome. Hum Mol Genet. 1995 Jun;4(6):1077-82. PMID:7655462
8. ↑ Park WJ, Meyers GA, Li X, Theda C, Day D, Orlow SJ, Jones MC, Jabs EW. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet. 1995 Jul;4(7):1229-33. PMID:8528214
9. ↑ Meyers GA, Day D, Goldberg R, Daentl DL, Przylepa KA, Abrams LJ, Graham JM Jr, Feingold M, Moeschler JB, Rawnsley E, Scott AF, Jabs EW. 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. Am J Hum Genet. 1996 Mar;58(3):491-8. PMID:8644708
10. ↑ Pulleyn LJ, Reardon W, Wilkes D, Rutland P, Jones BM, Hayward R, Hall CM, Brueton L, Chun N, Lammer E, Malcolm S, Winter RM. Spectrum of craniosynostosis phenotypes associated with novel mutations at the fibroblast growth factor receptor 2 locus. Eur J Hum Genet. 1996;4(5):283-91. PMID:8946174
11. ↑ Steinberger D, Mulliken JB, Muller U. Crouzon syndrome: previously unrecognized deletion, duplication, and point mutation within FGFR2 gene. Hum Mutat. 1996;8(4):386-90. PMID:8956050 doi:<386::AID-HUMU18>3.0.CO;2-Z 10.1002/(SICI)1098-1004(1996)8:4<386::AID-HUMU18>3.0.CO;2-Z
12. ↑ Oldridge M, Lunt PW, Zackai EH, McDonald-McGinn DM, Muenke M, Moloney DM, Twigg SR, Heath JK, Howard TD, Hoganson G, Gagnon DM, Jabs EW, Wilkie AO. Genotype-phenotype correlation for nucleotide substitutions in the IgII-IgIII linker of FGFR2. Hum Mol Genet. 1997 Jan;6(1):137-43. PMID:9002682
13. ↑ Steinberger D, Collmann H, Schmalenberger B, Muller U. A novel mutation (a886g) in exon 5 of FGFR2 in members of a family with Crouzon phenotype and plagiocephaly. J Med Genet. 1997 May;34(5):420-2. PMID:9152842
14. ↑ Passos-Bueno MR, Sertie AL, Richieri-Costa A, Alonso LG, Zatz M, Alonso N, Brunoni D, Ribeiro SF. Description of a new mutation and characterization of FGFR1, FGFR2, and FGFR3 mutations among Brazilian patients with syndromic craniosynostoses. Am J Med Genet. 1998 Jul 7;78(3):237-41. PMID:9677057
15. ↑ Steinberger D, Vriend G, Mulliken JB, Muller U. The mutations in FGFR2-associated craniosynostoses are clustered in five structural elements of immunoglobulin-like domain III of the receptor. Hum Genet. 1998 Feb;102(2):145-50. PMID:9521581
16. ↑ Everett ET, Britto DA, Ward RE, Hartsfield JK Jr. A novel FGFR2 gene mutation in Crouzon syndrome associated with apparent nonpenetrance. Cleft Palate Craniofac J. 1999 Nov;36(6):533-41. PMID:10574673
17. ↑ Kress W, Collmann H, Busse M, Halliger-Keller B, Mueller CR. Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses). Cytogenet Cell Genet. 2000;91(1-4):134-7. PMID:11173845 doi:56833
18. ↑ Tsai FJ, Yang CF, Wu JY, Tsai CH, Lee CC. Mutation analysis of Crouzon syndrome and identification of one novel mutation in Taiwanese patients. Pediatr Int. 2001 Jun;43(3):263-6. PMID:11380921
19. ↑ Kan SH, Elanko N, Johnson D, Cornejo-Roldan L, Cook J, Reich EW, Tomkins S, Verloes A, Twigg SR, Rannan-Eliya S, McDonald-McGinn DM, Zackai EH, Wall SA, Muenke M, Wilkie AO. Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Am J Hum Genet. 2002 Feb;70(2):472-86. Epub 2002 Jan 4. PMID:11781872 doi:10.1086/338758
20. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
21. ↑ Jabs EW, Li X, Scott AF, Meyers G, Chen W, Eccles M, Mao JI, Charnas LR, Jackson CE, Jaye M. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet. 1994 Nov;8(3):275-9. PMID:7874170 doi:http://dx.doi.org/10.1038/ng1194-275
22. ↑ Park WJ, Meyers GA, Li X, Theda C, Day D, Orlow SJ, Jones MC, Jabs EW. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet. 1995 Jul;4(7):1229-33. PMID:8528214
23. ↑ Meyers GA, Day D, Goldberg R, Daentl DL, Przylepa KA, Abrams LJ, Graham JM Jr, Feingold M, Moeschler JB, Rawnsley E, Scott AF, Jabs EW. 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. Am J Hum Genet. 1996 Mar;58(3):491-8. PMID:8644708
24. ↑ Passos-Bueno MR, Sertie AL, Richieri-Costa A, Alonso LG, Zatz M, Alonso N, Brunoni D, Ribeiro SF. Description of a new mutation and characterization of FGFR1, FGFR2, and FGFR3 mutations among Brazilian patients with syndromic craniosynostoses. Am J Med Genet. 1998 Jul 7;78(3):237-41. PMID:9677057
25. ↑ Tartaglia M, Di Rocco C, Lajeunie E, Valeri S, Velardi F, Battaglia PA. Jackson-Weiss syndrome: identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders. Hum Genet. 1997 Nov;101(1):47-50. PMID:9385368
26. ↑ Kaabeche K, Lemonnier J, Le Mee S, Caverzasio J, Marie PJ. Cbl-mediated degradation of Lyn and Fyn induced by constitutive fibroblast growth factor receptor-2 activation supports osteoblast differentiation. J Biol Chem. 2004 Aug 27;279(35):36259-67. Epub 2004 Jun 9. PMID:15190072 doi:10.1074/jbc.M402469200
27. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
28. ↑ Oldridge M, Lunt PW, Zackai EH, McDonald-McGinn DM, Muenke M, Moloney DM, Twigg SR, Heath JK, Howard TD, Hoganson G, Gagnon DM, Jabs EW, Wilkie AO. Genotype-phenotype correlation for nucleotide substitutions in the IgII-IgIII linker of FGFR2. Hum Mol Genet. 1997 Jan;6(1):137-43. PMID:9002682
29. ↑ Passos-Bueno MR, Sertie AL, Richieri-Costa A, Alonso LG, Zatz M, Alonso N, Brunoni D, Ribeiro SF. Description of a new mutation and characterization of FGFR1, FGFR2, and FGFR3 mutations among Brazilian patients with syndromic craniosynostoses. Am J Med Genet. 1998 Jul 7;78(3):237-41. PMID:9677057
30. ↑ Kan SH, Elanko N, Johnson D, Cornejo-Roldan L, Cook J, Reich EW, Tomkins S, Verloes A, Twigg SR, Rannan-Eliya S, McDonald-McGinn DM, Zackai EH, Wall SA, Muenke M, Wilkie AO. Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Am J Hum Genet. 2002 Feb;70(2):472-86. Epub 2002 Jan 4. PMID:11781872 doi:10.1086/338758
31. ↑ Park WJ, Theda C, Maestri NE, Meyers GA, Fryburg JS, Dufresne C, Cohen MM Jr, Jabs EW. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome. Am J Hum Genet. 1995 Aug;57(2):321-8. PMID:7668257
32. ↑ Ibrahimi OA, Eliseenkova AV, Plotnikov AN, Yu K, Ornitz DM, Mohammadi M. Structural basis for fibroblast growth factor receptor 2 activation in Apert syndrome. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7182-7. Epub 2001 Jun 5. PMID:11390973 doi:http://dx.doi.org/10.1073/pnas.121183798
33. ↑ Wilkie AO, Slaney SF, Oldridge M, Poole MD, Ashworth GJ, Hockley AD, Hayward RD, David DJ, Pulleyn LJ, Rutland P, et al.. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995 Feb;9(2):165-72. PMID:7719344 doi:http://dx.doi.org/10.1038/ng0295-165
34. ↑ Tsai FJ, Hwu WL, Lin SP, Chang JG, Wang TR, Tsai CH. Two common mutations 934C to G and 937C to G of fibroblast growth factor receptor 2 (FGFR2) gene in Chinese patients with Apert syndrome. Hum Mutat. 1998;Suppl 1:S18-9. PMID:9452027
35. ↑ Hatch NE, Hudson M, Seto ML, Cunningham ML, Bothwell M. Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F. J Biol Chem. 2006 Sep 15;281(37):27292-305. Epub 2006 Jul 14. PMID:16844695 doi:10.1074/jbc.M600448200
36. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
37. ↑ Chen H, Ma J, Li W, Eliseenkova AV, Xu C, Neubert TA, Miller WT, Mohammadi M. A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. Mol Cell. 2007 Sep 7;27(5):717-30. PMID:17803937 doi:http://dx.doi.org/10.1016/j.molcel.2007.06.028
38. ↑ Meyers GA, Day D, Goldberg R, Daentl DL, Przylepa KA, Abrams LJ, Graham JM Jr, Feingold M, Moeschler JB, Rawnsley E, Scott AF, Jabs EW. 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. Am J Hum Genet. 1996 Mar;58(3):491-8. PMID:8644708
39. ↑ Oldridge M, Lunt PW, Zackai EH, McDonald-McGinn DM, Muenke M, Moloney DM, Twigg SR, Heath JK, Howard TD, Hoganson G, Gagnon DM, Jabs EW, Wilkie AO. Genotype-phenotype correlation for nucleotide substitutions in the IgII-IgIII linker of FGFR2. Hum Mol Genet. 1997 Jan;6(1):137-43. PMID:9002682
40. ↑ Kress W, Collmann H, Busse M, Halliger-Keller B, Mueller CR. Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses). Cytogenet Cell Genet. 2000;91(1-4):134-7. PMID:11173845 doi:56833
41. ↑ Kan SH, Elanko N, Johnson D, Cornejo-Roldan L, Cook J, Reich EW, Tomkins S, Verloes A, Twigg SR, Rannan-Eliya S, McDonald-McGinn DM, Zackai EH, Wall SA, Muenke M, Wilkie AO. Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. Am J Hum Genet. 2002 Feb;70(2):472-86. Epub 2002 Jan 4. PMID:11781872 doi:10.1086/338758
42. ↑ Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet. 1995 Feb;9(2):108. PMID:7719333 doi:http://dx.doi.org/10.1038/ng0295-108
43. ↑ Rutland P, Pulleyn LJ, Reardon W, Baraitser M, Hayward R, Jones B, Malcolm S, Winter RM, Oldridge M, Slaney SF, et al.. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet. 1995 Feb;9(2):173-6. PMID:7719345 doi:http://dx.doi.org/10.1038/ng0295-173
44. ↑ Tartaglia M, Valeri S, Velardi F, Di Rocco C, Battaglia PA. Trp290Cys mutation in exon IIIa of the fibroblast growth factor receptor 2 (FGFR2) gene is associated with Pfeiffer syndrome. Hum Genet. 1997 May;99(5):602-6. PMID:9150725
45. ↑ Mathijssen IM, Vaandrager JM, Hoogeboom AJ, Hesseling-Janssen AL, van den Ouweland AM. Pfeiffer's syndrome resulting from an S351C mutation in the fibroblast growth factor receptor-2 gene. J Craniofac Surg. 1998 May;9(3):207-9. PMID:9693549
46. ↑ Passos-Bueno MR, Richieri-Costa A, Sertie AL, Kneppers A. Presence of the Apert canonical S252W FGFR2 mutation in a patient without severe syndactyly. J Med Genet. 1998 Aug;35(8):677-9. PMID:9719378
47. ↑ Cornejo-Roldan LR, Roessler E, Muenke M. Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. Hum Genet. 1999 May;104(5):425-31. PMID:10394936
48. ↑ Priolo M, Lerone M, Baffico M, Baldi M, Ravazzolo R, Cama A, Capra V, Silengo M. Pfeiffer syndrome type 2 associated with a single amino acid deletion in the FGFR2 gene. Clin Genet. 2000 Jul;58(1):81-3. PMID:10945669
49. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
50. ↑ Przylepa KA, Paznekas W, Zhang M, Golabi M, Bias W, Bamshad MJ, Carey JC, Hall BD, Stevenson R, Orlow S, Cohen MM Jr, Jabs EW. Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome. Nat Genet. 1996 Aug;13(4):492-4. PMID:8696350 doi:10.1038/ng0896-492
51. ↑ Wang TJ, Huang CB, Tsai FJ, Wu JY, Lai RB, Hsiao M. Mutation in the FGFR2 gene in a Taiwanese patient with Beare-Stevenson cutis gyrata syndrome. Clin Genet. 2002 Mar;61(3):218-21. PMID:12000365
52. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
53. ↑ Chen H, Ma J, Li W, Eliseenkova AV, Xu C, Neubert TA, Miller WT, Mohammadi M. A molecular brake in the kinase hinge region regulates the activity of receptor tyrosine kinases. Mol Cell. 2007 Sep 7;27(5):717-30. PMID:17803937 doi:http://dx.doi.org/10.1016/j.molcel.2007.06.028
54. ↑ McGillivray G, Savarirayan R, Cox TC, Stojkoski C, McNeil R, Bankier A, Bateman JF, Roscioli T, Gardner RJ, Lamande SR. Familial scaphocephaly syndrome caused by a novel mutation in the FGFR2 tyrosine kinase domain. J Med Genet. 2005 Aug;42(8):656-62. PMID:16061565 doi:10.1136/jmg.2004.027888
55. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
56. ↑ Lew ED, Bae JH, Rohmann E, Wollnik B, Schlessinger J. Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19802-7. Epub 2007 Dec 3. PMID:18056630
57. ↑ Rohmann E, Brunner HG, Kayserili H, Uyguner O, Nurnberg G, Lew ED, Dobbie A, Eswarakumar VP, Uzumcu A, Ulubil-Emeroglu M, Leroy JG, Li Y, Becker C, Lehnerdt K, Cremers CW, Yuksel-Apak M, Nurnberg P, Kubisch C, Schlessinger J, van Bokhoven H, Wollnik B. Mutations in different components of FGF signaling in LADD syndrome. Nat Genet. 2006 Apr;38(4):414-7. Epub 2006 Feb 26. PMID:16501574 doi:ng1757
58. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
59. ↑ Reardon W, Smith A, Honour JW, Hindmarsh P, Das D, Rumsby G, Nelson I, Malcolm S, Ades L, Sillence D, Kumar D, DeLozier-Blanchet C, McKee S, Kelly T, McKeehan WL, Baraitser M, Winter RM. Evidence for digenic inheritance in some cases of Antley-Bixler syndrome? J Med Genet. 2000 Jan;37(1):26-32. PMID:10633130
60. ↑ Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol. 2009 Aug;129(8):1861-7. doi: 10.1038/jid.2009.97. Epub 2009, Apr 23. PMID:19387476 doi:10.1038/jid.2009.97
61. ↑ Merrill AE, Sarukhanov A, Krejci P, Idoni B, Camacho N, Estrada KD, Lyons KM, Deixler H, Robinson H, Chitayat D, Curry CJ, Lachman RS, Wilcox WR, Krakow D. Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling. Am J Hum Genet. 2012 Mar 9;90(3):550-7. doi: 10.1016/j.ajhg.2012.02.005. Epub, 2012 Mar 1. PMID:22387015 doi:10.1016/j.ajhg.2012.02.005
62. ↑ Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996 Jun 21;271(25):15292-7. PMID:8663044
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79. ↑ Olsen SK, Li JY, Bromleigh C, Eliseenkova AV, Ibrahimi OA, Lao Z, Zhang F, Linhardt RJ, Joyner AL, Mohammadi M. Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain. Genes Dev. 2006 Jan 15;20(2):185-98. Epub 2005 Dec 29. PMID:16384934 doi:http://dx.doi.org/10.1101/gad.1365406
80. ↑ Olsen SK, Li JY, Bromleigh C, Eliseenkova AV, Ibrahimi OA, Lao Z, Zhang F, Linhardt RJ, Joyner AL, Mohammadi M. Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain. Genes Dev. 2006 Jan 15;20(2):185-98. Epub 2005 Dec 29. PMID:16384934 doi:http://dx.doi.org/10.1101/gad.1365406