Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation
Elisabeth Lajeuniea, Vincent El Ghouzzia, Martine Le Merrera, Arnold Munnicha, Jacky Bonaventurea, Dominique Renierb
a Unité de
Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393,
Institut Necker, Hôpital des Enfants Malades, 149 rue de Sèvres,
75743 Paris Cedex 15, France, b Département de Neurochirurgie Pédiatrique,
Hôpital des Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex
15, France
Correspondence to: Dr Bonaventure or Dr Renier.
Received 23 June 1998;
Revised version accepted for publication 7 September 1998
A recurrent point mutation in the fibroblast growth factor
receptor 3 (FGFR3) gene that converts proline 250 into arginine is
commonly associated with coronal craniosynostosis and has allowed definition of a new syndrome on a molecular basis. Sixty-two patients with sporadic or familial forms of coronal craniosynostosis were investigated for the P250R FGFR3 mutation. It was identified in 20 probands originating from 27 unrelated families (74%), while only 6/35
sporadic cases (17%) harboured the mutation. In both familial and
sporadic cases, females were significantly more severely affected than
males. Hence, while 68% of females carrying the P250R mutation showed
brachycephaly, only 35% of males had the same phenotype. In the most
severe forms of the disease, the association of bicoronal
craniosynostosis with hypertelorism and marked bulging of the temporal
fossae were common hallmarks that might be helpful for clinical diagnosis.
Taken together, these results indicate that the P250R FGFR3 mutation is
mostly familial and is associated with a more severe phenotype in
females than in males. The sex related severity of the condition points
to the possible implication of modifier genes in this syndrome.
Keywords: coronal craniosynostosis; P250R FGFR3 mutation; sex related expressivity
© 1999 by J Med Genet
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