Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Fibroblast growth factor receptor 3

The FGFR3 gene encodes an FGF receptor. Mutations of that gene cause several autosomal dominant dysmorphic disorders including achondroplasia and Crouzon syndrome.

Genetests:

Research Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Thanatophoric dysplasia 2
FGFR3
Thanatophoric dysplasia 1
FGFR3
Achondroplasia
FGFR3
Crouzon syndrome
FGFR3
Muenke syndrome
FGFR3

References:

1.

McKusick VA et al. (1973) Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.

[^]
2.

Superti-Furga A et al. (1995) A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.

[^]
3.

Bellus GA et al. (1995) Achondroplasia is defined by recurrent G380R mutations of FGFR3.

[^]
4.

Shiang R et al. (1994) Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.

[^]
5.

Rousseau F et al. (1994) Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.

[^]
6.

Huggins MJ et al. (1999) Achondroplasia-hypochondroplasia complex in a newborn infant.

[^]
7.

Chitayat D et al. (1999) Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.

[^]
8.

Henderson S et al. (2000) Germline and somatic mosaicism in achondroplasia.

[^]
9.

Sobetzko D et al. (2000) Achondroplasia with the FGFR3 1138g-->a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father.

[^]
10.

Yasoda A et al. (2004) Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.

[^]
11.

Van Esch H et al. (2004) Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg mutation in FGFR3.

[^]
12.

Rump P et al. (2006) Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.

[^]
13.

Heuertz S et al. (2006) Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.

[^]
14.

Natacci F et al. (2008) Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.

[^]
15.

Matsushita T et al. (2009) FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.

[^]
16.

Moloney DM et al. (1996) Exclusive paternal origin of new mutations in Apert syndrome.

[^]
17.

Meyers GA et al. (1995) Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.

[^]
18.

Arnaud-López L et al. (2007) Crouzon with acanthosis nigricans. Further delineation of the syndrome.

[^]
19.

Singh D et al. (2012) Transforming fusions of FGFR and TACC genes in human glioblastoma.

[^]
20.

Rohmann E et al. (2006) Mutations in different components of FGF signaling in LADD syndrome.

[^]
21.

Muenke M et al. (1997) A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.

[^]
22.

Reardon W et al. (1997) Craniosynostosis associated with FGFR3 pro250arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis.

[^]
23.

Golla A et al. (1997) Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.

[^]
24.

None (1997) Craniosynostosis: genes and mechanisms.

[^]
25.

Hollway GE et al. (1998) Deafness due to Pro250Arg mutation of FGFR3.

[^]
26.

Gripp KW et al. (1998) Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3.

[^]
27.

Lajeunie E et al. (1999) Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.

[^]
28.

Lowry RB et al. (2001) Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and sprengel shoulder with and without Pro250Arg mutation in the FGFR3 gene.

[^]
29.

Rannan-Eliya SV et al. (2004) Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.

[^]
30.

Mansour SL et al. (2009) Hearing loss in a mouse model of Muenke syndrome.

[^]
31.

Chen L et al. (2001) A Ser(365)-->Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia.

[^]
32.

Tavormina PL et al. (1995) Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.

[^]
33.

Tavormina PL et al. (1995) Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.

[^]
34.

Rousseau F et al. (1996) Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).

[^]
35.

Wilcox WR et al. (1998) Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia.

[^]
36.

Sawai H et al. (1999) Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.

[^]
37.

Brodie SG et al. (1999) Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.

[^]
38.

Pannier S et al. (2009) Thanatophoric dysplasia caused by double missense FGFR3 mutations.

[^]
39.

Lin T et al. (2003) A central nervous system specific mouse model for thanatophoric dysplasia type II.

[^]
40.

Li D et al. (2006) Thanatophoric dysplasia type 2 with encephalocele during the second trimester.

[^]
41.

Thompson LM et al. (1991) A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.

[^]
42.

Keegan K et al. (1991) Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3.

[^]
43.

None (1988) Bone dysplasia 'families'.

[^]
44.

Scotet E et al. (1995) The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific.

[^]
45.

Rousseau F et al. (1995) Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.

[^]
46.

Ikegawa S et al. (1995) Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients.

[^]
47.

Bellus GA et al. (1995) A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.

[^]
48.

Avraham KB et al. (1994) Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes.

[^]
49.

Prinos P et al. (1995) A common FGFR3 gene mutation in hypochondroplasia.

[^]
50.

Nishimura G et al. (1995) Atypical radiological findings in achondroplasia with uncommon mutation of the fibroblast growth factor receptor-3 (FGFR-3) gene (Gly to Cys transition at codon 375)

[^]
51.

Deng C et al. (1996) Fibroblast growth factor receptor 3 is a negative regulator of bone growth.

[^]
52.

Colvin JS et al. (1996) Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.

[^]
53.

Naski MC et al. (1996) Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia.

[^]
54.

von Gernet S et al. (1996) Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p.

[^]
55.

Bellus GA et al. (1996) Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes.

[^]
56.

Pokharel RK et al. (1996) Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene.

[^]
57.

Bergsagel PL et al. (1996) Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.

[^]
58.

Su WC et al. (1997) Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.

[^]
59.

Moloney DM et al. (1997) Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.

[^]
60.

Perez-Castro AV et al. (1997) Genomic organization of the human fibroblast growth factor receptor 3 (FGFR3) gene and comparative sequence analysis with the mouse Fgfr3 gene.

[^]
61.

Chesi M et al. (1997) Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.

[^]
62.

Lanning RW et al. (1997) An improved methodology for the detection of the common mutation in the FGFR3 gene responsible for achondroplasia.

[^]
63.

Prinster C et al. (1998) Comparison of clinical-radiological and molecular findings in hypochondroplasia.

[^]
64.

Deutz-Terlouw PP et al. (1998) Asn540Thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia.

[^]
65.

Paznekas WA et al. (1998) Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations.

[^]
66.

Graham JM et al. (1998) Syndrome of coronal craniosynostosis with brachydactyly and carpal/tarsal coalition due to Pro250Arg mutation in FGFR3 gene.

[^]
67.

Ramaswami U et al. (1998) Genotype and phenotype in hypochondroplasia.

[^]
68.

Naski MC et al. (1998) Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3.

[^]
69.

Angle B et al. (1998) Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association.

[^]
70.

Brodie SG et al. (1998) Thanatophoric dysplasia type I with syndactyly.

[^]
71.

Robin NH et al. (1998) Nonpenetrance in FGFR3-associated coronal synostosis syndrome.

[^]
72.

Li C et al. (1999) A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors.

[^]
73.

Tavormina PL et al. (1999) A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.

[^]
74.

El Ghouzzi V et al. (1999) Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.

[^]
75.

Grigelioniené G et al. (1998) A novel missense mutation Ile538Val in the fibroblast growth factor receptor 3 in hypochondroplasia. Mutations in brief no. 122. Online.

[^]
76.

Tsai FJ et al. (1999) Identification of a common N540K mutation in 8/18 Taiwanese hypochondroplasia patients: further evidence for genetic heterogeneity.

[^]
77.

Fofanova OV et al. (1998) A missense mutation of C1659 in the fibroblast growth factor receptor 3 gene in Russian patients with hypochondroplasia.

[^]
78.

Passos-Bueno MR et al. (1999) Clinical spectrum of fibroblast growth factor receptor mutations.

[^]
79.

Cappellen D et al. (1999) Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas.

[^]
80.

Tsai FJ et al. (1999) Mutations in the fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia, hypochondroplasia, and thanatophoric dysplasia: Taiwanese data.

[^]
81.

Chen L et al. (1999) Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis.

[^]
82.

Monsonego-Ornan E et al. (2000) The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.

[^]
83.

Henderson JE et al. (2000) Expression of FGFR3 with the G380R achondroplasia mutation inhibits proliferation and maturation of CFK2 chondrocytic cells.

[^]
84.

Kitoh H et al. (1998) Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia Type I. Mutations in brief no. 199. Online.

[^]
85.

Mortier G et al. (2000) Clinical and radiographic features of a family with hypochondroplasia owing to a novel Asn540Ser mutation in the fibroblast growth factor receptor 3 gene.

[^]
86.

Iwata T et al. (2000) A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos.

[^]
87.

Saito H et al. (2000) Prenatal DNA diagnosis of a single-gene disorder from maternal plasma.

[^]
88.

Bellus GA et al. (2000) Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.

[^]
89.

Shimizu A et al. (2001) A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells.

[^]
90.

Sibley K et al. (2001) Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.

[^]
91.

Jang JH et al. (2001) Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers.

[^]
92.

Iwata T et al. (2001) Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice.

[^]
93.

Roscioli T et al. (2001) Premature calvarial synostosis and epidermal hyperplasia (Beare-Stevenson syndrome-like anomalies) resulting from a P250R missense mutation in the gene encoding fibroblast growth factor receptor 3.

[^]
94.

Karoui M et al. (2001) No evidence of somatic FGFR3 mutation in various types of carcinoma.

[^]
95.

Intini D et al. (2001) Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).

[^]
96.

Kimura T et al. (2001) The incidence of thanatophoric dysplasia mutations in FGFR3 gene is higher in low-grade or superficial bladder carcinomas.

[^]
97.

Shimizu A et al. (2002) FGFR3 isoforms have distinct functions in the regulation of growth and cell morphology.

[^]
98.

None (2002) Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells.

[^]
99.

Rasmussen T et al. (2002) FGFR3 dysregulation in multiple myeloma: frequency and prognostic relevance.

[^]
100.

Lievens PM et al. (2003) The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum.

[^]
101.

Thauvin-Robinet C et al. (2003) Hypochondroplasia and stature within normal limits: another family with an Asn540Ser mutation in the fibroblast growth factor receptor 3 gene.

[^]
102.

Hyland VJ et al. (2003) Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia.

[^]
103.

Ibrahimi OA et al. (2004) Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.

[^]
104.

Valverde-Franco G et al. (2004) Defective bone mineralization and osteopenia in young adult FGFR3-/- mice.

[^]
105.

Cho JY et al. (2004) Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia.

[^]
106.

Su YN et al. (2004) Rapid detection of FGFR3 gene mutation in achondroplasia by DHPLC system-coupling heteroduplex and fluorescence-enhanced primer-extension analysis.

[^]
107.

Logié A et al. (2005) Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.

[^]
108.

Davidson D et al. (2005) Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis.

[^]
109.

Nowroozi N et al. (2005) Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric dysplasia phenotypes in PC12 cells.

[^]
110.

Wyrobek AJ et al. (2006) Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.

[^]
111.

Hafner C et al. (2006) Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.

[^]
112.

Toydemir RM et al. (2006) A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.

[^]
113.

Eswarakumar VP et al. (2007) Skeletal overgrowth is mediated by deficiency in a specific isoform of fibroblast growth factor receptor 3.

[^]
114.

Riley BM et al. (2007) Impaired FGF signaling contributes to cleft lip and palate.

[^]
115.

Wilkie AO et al. (2007) Clinical dividends from the molecular genetic diagnosis of craniosynostosis.

[^]
116.

Friez MJ et al. (2008) Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al.

[^]
117.

Leroy JG et al. (2007) Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.

[^]
118.

Zankl A et al. (2008) Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation.

[^]
119.

García-Vargas A et al. (2008) An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation.

[^]
120.

Almeida MR et al. (2009) Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding Fibroblast Growth Factor Receptor 3 (FGFR3) in Portugal.

[^]
121.

Salazar L et al. (2009) A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells.

[^]
122.

Goriely A et al. (2009) Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.

[^]
123.

Su N et al. (2010) Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.

[^]
124.

He L et al. (2010) Physical basis behind achondroplasia, the most common form of human dwarfism.

[^]
125.

He L et al. (2011) FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism.

[^]
126.

Barroso E et al. (2011) Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr.

[^]
127.

Jacky BP et al. (2013) Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A).

[^]
128.

Wang H et al. (2013) A novel missense mutation of FGFR3 in a Chinese female and her fetus with Hypochondroplasia by next-generation sequencing.

[^]
129.

Makrythanasis P et al. (2014) A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.

[^]
130.

Yamashita A et al. (2014) Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.

[^]
131.

NCBI article

NCBI 2261 [^]
132.

OMIM.ORG article

Omim 134934 [^]
133.

Orphanet article

Orphanet ID 121815 [^]
134.

Wikipedia article

Wikipedia EN (Fibroblast_growth_factor_receptor_3) [^]
Update: April 29, 2019