The Genetic Studies Of Syndromic Craniosynostosis And The Pathogenesis Of Carpenter Syndrome

Background and ObjectiveCongenital craniosynostosis is a common form of craniofacial bone deformities,In this study,the whole-exome sequencing was used to identify pathogenic mutations in five Chinese Han population cases of craniostenosis children,Carpenter syndrome is one kind of syndromic craniosynostosis,researchers have found MEGF8 mutations to be the cause of Carpenter syndrome subtype 2,and Megf8 is a modifier of BMP signaling in trigeminal sensory neurons.As we all know,BMP signaling pathway also plays a crucial role in the regulation of osteogenic differentiation,so we supposed that Megf8 is a modifier of BMP signaling in MC3T3-E1 osteogenic differentiation.MethodsApply high-throughput whole-exome sequencing(WES)on peripheral blood nucleated cell gene from 5 cases of craniosynostosis,and use the Sanger sequencing to authenticate the mutations found by WES,Transport slow virus transfection technical knockout Megf8 gene,RT-PCR detect change of the genes after Megf8 knockout.ResultsBioinformatics analysis of WES data and validation with Sanger sequencing,eventually found one mutation in each case,and one mutation was first reported at home and abroad;After knockout Megf8,alizarin red staining showed that cell line osteogenetic differentiation efficiency is reduced,at the same time RT-PCR detected BMP4,BMP2,RUNX2,Ocn and Opn expression decreasedConclusionsWith the aid of WES and combined with clinical features,case 1 and cas e2 were diagnosed as Saethre-Chotzen syndrome caused by TWIST1 mutations;case 3 and case 4 were diagnosed as Crouzon syndrome caused by Fibro blast Growth Factor Receptor2(FGFR2)mutations,case5 were diagnosed as Apert syndrome caused by FGFR2 mutation;Megf8 involved in osteogenesis differentiation process,and symmetric distribution the positive regulatory role differentiation process,its molecular mechanism is by influencing the BMP signaling pathway,which is Megf8 mutations can lead to the molecular mecha nism of cranial suture early Carpenter syndrome...