title: Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome.
abstract: Beare-Stevenson cutis gyrata syndrome (MIM 123790) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Many of these features are characteristic of some of the autosomal dominant craniosynostotic syndromes. Mutations in Crouzon, Jackson-Weiss, Pfeiffer and Apert syndromes have been reported in the FGFR2 extracellular domain. In Crouzon syndrome patients with acanthosis nigricans, a recurrent mutation occurs in the transmembrane domain of FGFR3. We now describe the detection of FGFR2 mutations in the Beare-Stevenson cutis gyrata syndrome. In three sporatic cases, a novel missense mutation was found causing an amino acid to be replaced by a cysteine; two had the identical Ty375Cys mutation in the transmembrane domain and one had a Ser372Cys mutation in the carboxyl-terminal end of the linker region between the immunoglobulin III-like (Iglll) and transmembrane domains. In two patients, neither of these mutations were found suggesting further genetic heterogeneity.
authors.affiliation: Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Przylepa
authors.forename: W
authors.initials: W
authors.lastname: Paznekas
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Golabi
authors.forename: W
authors.initials: W
authors.lastname: Bias
authors.forename: M J
authors.initials: MJ
authors.lastname: Bamshad
authors.forename: J C
authors.initials: JC
authors.lastname: Carey
authors.forename: B D
authors.initials: BD
authors.lastname: Hall
authors.forename: R
authors.initials: R
authors.lastname: Stevenson
authors.forename: S
authors.initials: S
authors.lastname: Orlow
authors.forename: M M
authors.initials: MM
authors.lastname: Cohen
authors.forename: E W
authors.initials: EW
authors.lastname: Jabs
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000052:Acanthosis Nigricans / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D003398:Craniosynostoses / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D012868:Skin Abnormalities; D013577:Syndrome
chemical_list: D017931:DNA Primers; D008562:Membrane Glycoproteins; D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2