Genetic research on five children with craniostenosis

Abstract

Objective To conduct clinical molecular diagnosis for Chinese Han nationality children with craniostenosis in order to find the related pathogenic genes. Methods Five children with craniostenosis admitted to the Department of Neurosurgery, Shanghai Children’s Medical Center of Shanghai Jiao Tong University conducted whole-exome sequencing (WES) on peripheral blood nucleated cell genes using the high-throughput WES between February 2014 and January 2015. The obtained data were used conduct bioinformatic information analysis, and Sanger sequencing was used to validate the gene related mutation found by WES. Results The exon 1 of the regulator of epithelial-mesenchymal transition TWIST1 of 2 children had a heterozygous missense mutation respectively: c. 528C>G, p. Ser176Arg和c.487C>T, p.Leu163Phe; the other 3 children had a fibroblast growth factor receptor 2 (FGFR2) gene heterozygous missense mutation respectively. Two of them were located in the exon 7 (c.755C>G, p. Ser252Trp and c. 833G>T, p. Cys278Phe); and 1 was located in the exon 8 (c.1 012G>C, p. Gly338Arg). Conclusions With the aid of high-throughput DNA sequencing technology and combined with clinical features, 2 children were diagnosed as Saethre-Chotzen syndrome caused by TWIST1 mutation; 2 were diagnosed as Crouzon syndrome caused by FGFR2 mutation, and 1 was diagnosed as Apert syndrome caused by FGFR2 mutation. Genetic studies contribute to diagnose the children with craniostenosis whose clinical feature is not significant, and provide the basis for the diagnosis of craniostenosis and typing. Key words: Receptor, fibroblast growth factor, type 2; Exome; Sequence analysis, DNA; Point mutation; TWIST1; Craniosynostoses