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Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.
Nat Genet. 1995 Dec; 11(4):462-4.NGen

Abstract

Crouzon syndrome, an autosomal dominant condition characterized by craniosynostosis, ocular proptosis and midface hypoplasia, is associated with mutations in fibroblast growth factor receptor 2 (FGFR2) (refs 1-3). For example, we have identified 10 different mutations in the FGFR2 extracellular immunoglobulin III (IgIII) domain in 50% (16/32) of our Crouzon syndrome patients. All mutations described so far for other craniosynostotic syndromes with associated limb anomalies--Jackson-Weiss, Pfeiffer, and Apert--also occur in the extracellular domain of FGFR2, as well as FGFR1 for Pfeiffer syndrome. In contrast, only FGFR3 mutations have been reported in dwarfing conditions--achondroplasia, thanatophoric dysplasia, and hypochondroplasia. For achondroplasia, greater than 99% of mutations occur in the FGFR3 transmembrane domain. We now report the unexpected observation of a FGFR3 transmembrane domain mutation, Ala391Glu, in three unrelated families with Crouzon syndrome and acanthosis nigricans, a specific skin disorder of hyperkeratosis and hyperpigmentation. The association of non-dwarfing and even non-skeletal conditions with FGFR3 mutations reveals the potential for a wide range of FGFR pleiotropic effects as well as locus heterogeneity in Crouzon syndrome. Our study underscores the biologic complexity of the FGFR gene family.

Authors+Show Affiliations

Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland 21287-3914, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7493034

Citation

Meyers, G A., et al. "Fibroblast Growth Factor Receptor 3 (FGFR3) Transmembrane Mutation in Crouzon Syndrome With Acanthosis Nigricans." Nature Genetics, vol. 11, no. 4, 1995, pp. 462-4.
Meyers GA, Orlow SJ, Munro IR, et al. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet. 1995;11(4):462-4.
Meyers, G. A., Orlow, S. J., Munro, I. R., Przylepa, K. A., & Jabs, E. W. (1995). Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nature Genetics, 11(4), 462-4.
Meyers GA, et al. Fibroblast Growth Factor Receptor 3 (FGFR3) Transmembrane Mutation in Crouzon Syndrome With Acanthosis Nigricans. Nat Genet. 1995;11(4):462-4. PubMed PMID: 7493034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. AU - Meyers,G A, AU - Orlow,S J, AU - Munro,I R, AU - Przylepa,K A, AU - Jabs,E W, PY - 1995/12/1/pubmed PY - 1995/12/1/medline PY - 1995/12/1/entrez SP - 462 EP - 4 JF - Nature genetics JO - Nat. Genet. VL - 11 IS - 4 N2 - Crouzon syndrome, an autosomal dominant condition characterized by craniosynostosis, ocular proptosis and midface hypoplasia, is associated with mutations in fibroblast growth factor receptor 2 (FGFR2) (refs 1-3). For example, we have identified 10 different mutations in the FGFR2 extracellular immunoglobulin III (IgIII) domain in 50% (16/32) of our Crouzon syndrome patients. All mutations described so far for other craniosynostotic syndromes with associated limb anomalies--Jackson-Weiss, Pfeiffer, and Apert--also occur in the extracellular domain of FGFR2, as well as FGFR1 for Pfeiffer syndrome. In contrast, only FGFR3 mutations have been reported in dwarfing conditions--achondroplasia, thanatophoric dysplasia, and hypochondroplasia. For achondroplasia, greater than 99% of mutations occur in the FGFR3 transmembrane domain. We now report the unexpected observation of a FGFR3 transmembrane domain mutation, Ala391Glu, in three unrelated families with Crouzon syndrome and acanthosis nigricans, a specific skin disorder of hyperkeratosis and hyperpigmentation. The association of non-dwarfing and even non-skeletal conditions with FGFR3 mutations reveals the potential for a wide range of FGFR pleiotropic effects as well as locus heterogeneity in Crouzon syndrome. Our study underscores the biologic complexity of the FGFR gene family. SN - 1061-4036 UR - https://wwww.unboundmedicine.com/medline/citation/7493034/Fibroblast_growth_factor_receptor_3__FGFR3__transmembrane_mutation_in_Crouzon_syndrome_with_acanthosis_nigricans_ L2 - http://dx.doi.org/10.1038/ng1295-462 DB - PRIME DP - Unbound Medicine ER -