title: Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome.
abstract: Pfeiffer syndrome (PS) is an autosomal dominant skeletal disorder which affects the bones of the skull, hands and feet. Previously, we have mapped PS in a subset of families to chromosome 8cen by linkage analysis and demonstrated a common mutation in the fibroblast growth factor receptor-1 (FGFR1) gene in the linked families. Here we report a second locus for PS on chromosome 10q25, and present evidence that mutations in the fibroblast growth factor receptor-2 (FGFR2) gene on 10q25 cause PS in an additional subset of familial and sporadic cases. Three different point mutations in FGFR2, which alter the same acceptor splice site of exon B, were observed in both sporadic and familial PS. In addition, a T to C transition in exon B predicting a cysteine to arginine substitution was identified in three sporadic PS individuals. Interestingly, this T to C change is identical to a mutation in FGFR2 previously reported in Crouzon syndrome, a phenotypically similar disorder but one lacking the hand and foot anomalies seen in PS. Our results highlight the genetic heterogeneity in PS and suggest that the molecular data will be an important complement to the clinical phenotype in defining craniosynostosis syndromes.
authors.affiliation: Children's Hospital of Philadelphia, Division of Human Genetics and Molecular Biology, Pennsylvania 19104-4399, USA.
authors.forename: U
authors.initials: U
authors.lastname: Schell
authors.forename: A
authors.initials: A
authors.lastname: Hehr
authors.forename: G J
authors.initials: GJ
authors.lastname: Feldman
authors.forename: N H
authors.initials: NH
authors.lastname: Robin
authors.forename: E H
authors.initials: EH
authors.lastname: Zackai
authors.forename: C
authors.initials: C
authors.lastname: de Die-Smulders
authors.forename: D H
authors.initials: DH
authors.lastname: Viskochil
authors.forename: J M
authors.initials: JM
authors.lastname: Stewart
authors.forename: G
authors.initials: G
authors.lastname: Wolff
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D003398:Craniosynostoses / Q000235:genetics*; D005091:Exons; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics; D008040:Genetic Linkage; D006228:Hand Deformities, Congenital / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013577:Syndrome
chemical_list: D017468:Receptors, Fibroblast Growth Factor