differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis细胞外的微分表达式matrix-mediated通路single-suture颅缝早闭.pdfVIP

Differential Expression of Extracellular Matrix-Mediated Pathways in Single-Suture Craniosynostosis 1 1 2 2 2 Brendan D. Stamper *, Sarah S. Park , Richard P. Beyer , Theo K. Bammler , Frederico M. Farin , Brig Mecham3, Michael L. Cunningham1,4 1 Center for Tissue and Cell Sciences, Seattle Children’s Research Institute, Seattle, Washington, United States of America, 2 Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, United States of America, 3 Sage Bionetworks, Seattle, Washington, United States of America, 4 Division of Craniofacial Medicine and the Department of Pediatrics, University of Washington, Seattle, Washington, United States of America Abstract Craniosynostosis is a disease defined by premature fusion of one or more cranial sutures. The mechanistic pathology of single-suture craniosynostosis is complex and while a number of genetic biomarkers and environmental predispositions have been identified, in many cases the causes remain controversial and inconclusive. In this study, gene expression data from 199 patients with isolated sagittal (n = 100), unilateral coronal (n = 50), and metopic (n = 49) synostosis are compared against both a control population (n = 50), as well as each other. After controlling for variables contributing to potential bias, FGF7, SFRP4, and VCAM1 emerged as genes associated with single-suture craniosynostosis due to their significantly large changes in gene expression compared to the control population. Pathway analysis implicated focal adhesion and extracellular matrix (ECM)-receptor interaction as differentially regulated gene networks when comparing all cases of single- suture