Clinicogenetic Study of Turkish Patients With Syndromic Craniosynostosis and Literature Review

NUR B., Pehlivanoglu S., MIHÇI E., Caliskan M., Demir D., ALPER Ö., ...More

PEDIATRIC NEUROLOGY, vol.50, no.5, pp.482-490, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 50 Issue: 5
  • Publication Date: 2014
  • Doi Number: 10.1016/j.pediatrneurol.2014.01.023
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.482-490
  • Istanbul University Affiliated: Yes


BACKGROUND: Fibroblast growth factor receptor 2 mutations have been associated with the craniosynostotic conditions of Apert, Crouzon, Pfeiffer, Saethre-Chotzen, Jackson-Weiss, Beare-Stevenson cutis gyrata, and Antley-Bixler syndromes in various ethnic groups. METHODS: Thirty-three unrelated Turkish patients (12 with Apert syndrome, 14 with Crouzon syndrome, six with Pfeiffer syndrome, and one with Saethre-Chotzen syndrome) and 67 nonsyndromic craniosynostosis patients were screened for mutations in exons Ilia and IIIc of the FGFR2 gene by denaturing high-performance liquid chromatography and confirmed by direct sequencing. RESULTS: We detected several pathogenic mutations in 11/33 (33%) patients with Apert syndrome (four with p.Pro253Arg; seven with p.Ser252Trp) and 8/33 (24%) patients with Crouzon syndrome (three with p.Trp290Arg, one with p.Cys342Tyr, p.Cys278Phe, p.G1n289Pro, and a novel p.Tyr340Asn mutation) and five (15%) with Pfeiffer syndrome (p.Cys342Arg, p.Pro253Arg, p.Trp290Arg, and p.Ser351Cys). No FGFR2 gene mutation was detected in any of the patients with Saethre-Chotzen syndrome and nonsyndromic craniosynostosis. CONCLUSIONS: Our results indicate that the majority of Turkish patients with syndromic craniosynostosis have detectable genetic changes with an overall frequency of 72.7%. Because this is the first molecular genetic report from a Turkish cohort, the identified spectrum profile of FGFR2 mutations of the syndromic craniosynostotic patients would be very helpful for understanding the genotype phenotype relationship and has a great value for diagnosis, prognosis, and genetic counseling.