Mutations in FGFR1 and FGFR2 cause familial and sporadic Pfeiffer syndrome |
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| Authors: | Schell, Ute Hehr, Andreas Feldman, George J. Robin, Nathaniel H. Zackai, Elaine H. de Die-Smulders, Christine Viskochil, David H. Stewart, Janet M. Wolff, Gerhard Ohashi, Hirofumi Price, R. Arlen Cohen, M.Michael, Jr. Muenke, Maximilian |
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| Affiliation: | 1Children's Hospital of Philadelphia, Division of Human Genetics and Molecular Biology, and Departments of Pediatrics Philadelphia, Pennsylvania 19104–4399, USA 2Departments of Genetics, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania 19104–4399, USA 3Departments of Psychiatry, University of Pennsylvania School of Medicine Philadelphia, Pennsylvania 19104–4399, USA 4Department of Clinical Genetics, Academical Hospital Maastricht Maastricht, The Netherlands 5Department of Pediatrics, Division of Medical Genetics, University of Utah Salt Lake City, Utah 84112 6Children's Hospital Division of Genetics Denver, Colorado 80218, USA 7Institut für Humangenetik der Universität Freiburg Freiburg, Germany 8Division of Medical Genetics, Saitama Children's Medical Center Saitama, Japan 9Department of Oral Biology, Faculty of Dentistry, and Department of Pediatrics, Faculty of Medicine, Dalhousie University Halifax Nova Scotia B3H 3J5, Canada |
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| Abstract: | Pfeifter syndrome (PS) is an autosomal dominant skeletal disorderwhich affects the bones of the skull, hands and feet. Previously,we have mapped PS in a subset of families to chromosome 8cenby linkage analysis and demonstrated a common mutation in thefibroblast growth factor receptor-1 (FGFR1) gene in the linkedfamilies. Here we report a second locus for PS on chromosome10q25, and present evidence that mutations in the fibroblastgrowth factor receptor-2 (FGFR2) gene on 10q25 cause PS in anadditional subset of familial and sporadic cases. Three differentpoint mutations in FGFR2, which alter the same acceptor splicesite of exon B, were observed in both sporadic and familialPS. In addition, a T to C transition in exon B predicting acysteine to arginine substitution was identified in three sporadicPS individuals. Interestingly, this T to C change is identicalto a mutation in FGFR2 previously reported in Crouzon syndrome,a phenotypically similar disorder but one lacking the hand andfoot anomalies seen in PS. Our results highlight the geneticheterogeneity in PS and suggest that the molecular data willbe an important complement to the clinical phenotype in definingcraniosynostosis syndromes. |
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