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Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability.
Hum Mol Genet. 1995 Jul; 4(7):1229-33.HM

Abstract

Mutations have been reported for several craniosynostotic disorders in exon IIIa (exon U or 7) or IIIc (exon B or 9) of the fibroblast growth factor receptor 2 gene (FGFR2). Among the conditions with FGFR2 mutations are two autosomal dominant syndromes, Crouzon and Jackson-Weiss. In this study, 24 Crouzon and one Jackson-Weiss syndrome patients were screened for mutations in the two exons by direct sequencing, and mutations were detected in 28% (7/25) of all cases. Five different mutations were found including two novel (W290G, C342W) and two previously reported, recurrent mutations for Crouzon syndrome (A344A, S354C), and one new mutation for Jackson-Weiss syndrome (C342R). The W290G mutation was found in exon IIIa which is common to both alternatively spliced forms of FGFR2, BEK (expressed predominantly in primordial bones) and KGFR (expressed preferentially in epithelia). Atypical Crouzon syndrome features of epithelial-derived anal and/or external ear anomalies were present in the two affected family members with the mutation. This phenotype possibly reflects the expression of both mutant BEK and KGFR. In addition, the Jackson-Weiss syndrome mutation, C342R, in exon IIIc was observed previously in other craniosynostotic syndromes, Crouzon and Pfeiffer. These results underscore the allelic heterogeneity of these conditions and the complexity of the phenotypic consequences of FGFR2 mutations.

Authors+Show Affiliations

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

8528214

Citation

Park, W J., et al. "Novel FGFR2 Mutations in Crouzon and Jackson-Weiss Syndromes Show Allelic Heterogeneity and Phenotypic Variability." Human Molecular Genetics, vol. 4, no. 7, 1995, pp. 1229-33.
Park WJ, Meyers GA, Li X, et al. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet. 1995;4(7):1229-33.
Park, W. J., Meyers, G. A., Li, X., Theda, C., Day, D., Orlow, S. J., Jones, M. C., & Jabs, E. W. (1995). Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Human Molecular Genetics, 4(7), 1229-33.
Park WJ, et al. Novel FGFR2 Mutations in Crouzon and Jackson-Weiss Syndromes Show Allelic Heterogeneity and Phenotypic Variability. Hum Mol Genet. 1995;4(7):1229-33. PubMed PMID: 8528214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. AU - Park,W J, AU - Meyers,G A, AU - Li,X, AU - Theda,C, AU - Day,D, AU - Orlow,S J, AU - Jones,M C, AU - Jabs,E W, PY - 1995/7/1/pubmed PY - 1995/7/1/medline PY - 1995/7/1/entrez SP - 1229 EP - 33 JF - Human molecular genetics JO - Hum Mol Genet VL - 4 IS - 7 N2 - Mutations have been reported for several craniosynostotic disorders in exon IIIa (exon U or 7) or IIIc (exon B or 9) of the fibroblast growth factor receptor 2 gene (FGFR2). Among the conditions with FGFR2 mutations are two autosomal dominant syndromes, Crouzon and Jackson-Weiss. In this study, 24 Crouzon and one Jackson-Weiss syndrome patients were screened for mutations in the two exons by direct sequencing, and mutations were detected in 28% (7/25) of all cases. Five different mutations were found including two novel (W290G, C342W) and two previously reported, recurrent mutations for Crouzon syndrome (A344A, S354C), and one new mutation for Jackson-Weiss syndrome (C342R). The W290G mutation was found in exon IIIa which is common to both alternatively spliced forms of FGFR2, BEK (expressed predominantly in primordial bones) and KGFR (expressed preferentially in epithelia). Atypical Crouzon syndrome features of epithelial-derived anal and/or external ear anomalies were present in the two affected family members with the mutation. This phenotype possibly reflects the expression of both mutant BEK and KGFR. In addition, the Jackson-Weiss syndrome mutation, C342R, in exon IIIc was observed previously in other craniosynostotic syndromes, Crouzon and Pfeiffer. These results underscore the allelic heterogeneity of these conditions and the complexity of the phenotypic consequences of FGFR2 mutations. SN - 0964-6906 UR - https://www.unboundmedicine.com/medline/citation/8528214/Novel_FGFR2_mutations_in_Crouzon_and_Jackson_Weiss_syndromes_show_allelic_heterogeneity_and_phenotypic_variability_ L2 - https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/4.7.1229 DB - PRIME DP - Unbound Medicine ER -