ABSTRACT

Craniosynostosis is a craniofacial malformation in which one or more sutures of the cranial vault are fused prematurely. It is estimated that craniosynostosis affects 1 in 2,000 to 2,500 live births worldwide. Early and accurate diagnosis of craniosynostosis is very important since premature suture closure causes not only a deformity of skull but also can directly affect the development of brain. Craniosynostosis occurs in all racial groups and more than 70% of all cases are non-syndromic. Until now, mutations in genes such as TWIST, EFNB1, FGFR1, FGFR2 and FGFR3 have been shown to play a role in craniosynostosis, whereas genetic factors of non-syndromic cases have not been fully identified yet.The aim of this study is to identify novel genes and gene regions for non-syndromic craniosynostosis cases by utilizing a genetic approach and a high resolution aCGH. Out of 10 patients included in this study, two patients were diagnosed with Craniofrontonasal syndrome and Apert syndrome, respectively. For these two patients, molecular analysis of EFNB1 and FGFR2 genes were carried out using Sanger sequencing. The patient diagnosed with Craniosynostosis syndrome has been shown to carry a novel mutation. The other patient carried one of the most common mutations of FGFR2; c.755 C>G. For the remaining 8 non-syndromic cases, aCGH analysis was performed by using microarray chips at 5.3KB resolution (SurePrint G3 Human CGH Microarray Kit, 2x400K, Agilent Technologies), and various deletions and duplications were detected. Overall, this study provides insights into the genetic determinants of craniosynostosis, which will contribute to the future studies in the field.