Phenotypic expression ofthefibroblast growth factor receptor3(FGFR3)mutation P250Rina large craniosynostosis family

The craniosynostosis syndromesarea heterogeneous groupofsporadic, autosomaldominant disorders withsignificant clinical overlap. Recently, we described a largefamilywithautosomaldominant craniosynostosis suggestive ofSaethreChotzen syndrome, inwhichlinkage tothe Saethre-Chotzen syndrome loci on7phad beenexcluded. We nowreportthepresence ofamutationinthefibroblast growthfactor receptor3(FGFR3)inthis family. Themutation, P250R,hadbeenpreviously reported in10 patients withnon-syndromic craniosynostosis. Variable expression ofthismutation isevidentespecially in two additional membersofthisfamily, oneofwhom is severely affected withpancraniosynostosis. Thefamily provides afurther exampleof genetic heterogeneity andvariable expressionofthecraniosynostosis syndromes andbroadensthephenotypic spectrum associated withtheFGFR3 mutation P250R.Inaddition, wefoundapolymorphism(F384L)in thetransmembrane domainofFGFR3 whichoccurswitha frequency of3%intheTurkish population butisuncommonamongGermans. (_JMed Genet1997;34:683-684)