Identification of causative mutation in a Korean family with Crouzon syndrome using whole exome sequencing

Craniosynostosis is a heterogeneous disorder that results in a common malformation which causes premature fusion of one or more cranial sutures. Whole-exome sequencing (WES) was recently developed as a powerful genetic strategy for identifying pathogenic mutations of heterogeneous disorders with various causative genes. A 24-year-old woman visited our department for evaluation of persistent hearing impairment and absence of an external auditory canal from birth. In this study, we performed WES to identify the causative mutation in a Korean family who has Crouzon Syndrome (CS). We first focused on 16 genes associated with craniosynostosis and sorted the heterozygous variations according to the autosomal dominant inheritance pattern of her family. After the bioinformatic analysis for filtering and detecting variations, three non-synonymous variations in different genes were selected for additional analysis. Among these, the p.C278F mutation in the FGFR2 gene was only absent from both dbSNP and the 1000 Genomes database. We considered the p.C278F mutation in the FGFR2 gene as the causative mutation for the CS. This result suggests that the application of WES will be valuable for diagnosis of congenital disorders with clinical and genetics heterogeneities.