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Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome

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When normal development and growth of the calvarial sutures is disrupted, craniosynostosis (premature calvarial suture fusion) may result. Classical craniosynostosis syndromes are autosomal dominant traits and include Apert, Pfeiffer, Crouzon, Jackson–Weiss, and Saethre–Chotzen syndromes. In these conditions, there is premature fusion of skull bones leading to an abnormal head shape, ocular hypertelorism with proptosis, and midface hypoplasia. It is known that mutations in the fibroblast growth factor receptors 1, 2, and 3 cause craniosynostosis. We report on a child with a clinically diagnosed Pfeiffer syndrome that shows the missense point mutation Q289P in exon 8 of the FGFR2 gene. This is a mutation not previously described in the Pfeiffer syndrome but reported in the Crouzon, Jackson–Weiss, and Saethre–Chotzen syndromes. In this paper, we propose the concept that these disorders may represent one genetic condition with phenotypic variability.

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Fig. 1
Fig. 2
Fig. 3


FGFR 1-2-3 :

fibroblast growth factor receptor 1, 2, 3 genes


twist transcription factor 1 gene

MSX2 :

muscle segment homeobox gene 2

EFNB 1 :

ephrin B1 gene


L1 cell adhesion molecule gene


immune globulin like domain II and III


amino acid substitution serine in tryptophan


amino acid substitution proline in arginine


amino acid substitution glutamine in proline


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Correspondence to Maria Piccione.

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Piccione, M., Antona, V., Niceta, M. et al. Q289P mutation in the FGFR2 gene: first report in a patient with type 1 Pfeiffer syndrome. Eur J Pediatr 168, 1135–1139 (2009).

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