RESUMO
Objective@#Reveal the global expression profile of serum exosomal proteins of Crouzon syndrome patients.@*Methods@#We isolated microvesicles from serum of Crouzon children with a C342Y mutation in FGFR2 by ultracentrifugation, which were further characterized by electron microscopy and immunoblotting. The protein profiling in normal subjects and Crouzon patients was systematically compared by iTRAQ proteomic analysis.@*Results@#The result demonstrated that microvesicles were between 30—100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total number of 62 proteins, among which 22 proteins overlap with ExoCarta database and were different between the Crouzon patient and the normal subject. The Ingenuity Pathway Analysis showed that the functions of these proteins are mostly involved in Developmental Disorder, Hereditary Disorder, Skeletal and Muscular Disorders, which are all related to the clinical manifestations of Crouzon syndrome. In addition, the proteins were focused on the network of "Organismal Injury and Abnormalities, Hematological System Development and Function, Cell-To-Cell Signaling and Interaction" . The central protein FN1 was presented as the key protein in the network.@*Conclusions@#Our data demonstrated that serum exosomes harbor informative proteins and FN1 was selected as a potential candidate for its role in promoting osteoblast adhesion, proliferation and mineralization.
RESUMO
Crouzon syndrome is an autosomal dominant craniosynostosis syndrome caused by mutation in the fibroblast growth factor receptor 2 (FGFR-2). Numerous findings from animal studies imply a critical role for FGFRs in the regulation of skeletal development. Here, we report 2 unrelated patients with Crouzon syndrome accompanied by elbow deformity. Subsequently, we analyzed the sequence of the FGFR2 gene and found that both of the patients carried the Cys342Arg mutation. The findings suggest that the C342R mutation in FGFR2 may cause Crouzon syndrome and elbow deformity in Chinese patients.
