Molecular genetic approach to craniosynostosis patients and whole genom array CGH analysis of nonsyndromic cases

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 the skull but also can directly affect the development of the brain. Craniosynostosis occurs in all racial groups and more than 70% of all cases are non-syndromic. Until now, mutations such as TWIST, EFNB1, FGFR1, FGFR2 and FGFR3 are shown to play role in craniosynostosis, whereas genetic factors of non-syndromic cases haven’t been fully identified yet.

The aim of this study is to identify novel genes and gene regions for non-syndromic craniosynostosis cases through utilizing a genetic approach to craniosynostosis cases and a high-resolution aCGH technique.

Out of 10 patients included in the study, 2 patients were diagnosed with Craniosynostosis syndrome and Apert syndrome. For these patients, molecular analyses of EFNB1 and FGFR2 gene were carried out using Sanger sequencing. A patient diagnosed with Craniosynostosis syndrome has been shown to carry a novel mutation. Our other patient has been demonstrated to have one of the most common mutations of FGFR2; c.755 C>G. For the remaining 8 non-syndromic cases, `SurePrint G3 Human CGH Microarray Kit, 2x400K (Agilent Technologies) ` microarray chips, which are made up of 60 mer-long 411.056 probes with 5.3KB resolution, were used to perform aCGH analysis and various deletions and duplications were detected. Results of this study are estimated to provide preliminary information about pathways playing role in the pathogenesis of craniosynostosis, which contribute to further studies in the field.