%0 Journal Article
%T Unique Sex-Based Approach Identifies Transcriptomic Biomarkers Associated with Non-Syndromic Craniosynostosis
%A Brendan D. Stamper
%A Sarah S. Park
%A Richard P. Beyer
%A Theo K. Bammler and Michael L. Cunningham
%J Gene Regulation and Systems Biology
%D 2012
%I 
%R 10.4137/GRSB.S9693
%X Background: The premature fusion of one cranial suture, also referred to as non-syndromic craniosynostosis, most commonly involves premature fusion of the sagittal, coronal, or metopic sutures, in that order. Population-based epidemiological studies have found that the birth prevalence of single-suture craniosynostosis is both suture- and sex-dependent. Methods: Transcriptomic data from 199 individuals with isolated sagittal (n = 100), unilateral coronal (n = 50), and metopic (n = 49) synostosis were compared against a control population (n = 50) to identify transcripts accounting for the different sex-based frequencies observed in this disease. Results: Differential sex-based gene expression was classified as either gained (divergent) or lost (convergent) in affected individuals to identify transcripts related to disease predilection. Divergent expression was dependent on synostosis sub-type, and was extensive in metopic craniosynostosis specifically. Convergent microarray-based expression was independent of synostosis sub-type, with convergent expression of FBN2, IGF2BP3, PDE1C and TINAGL1 being the most robust across all synostosis sub-types. Conclusions: Analysis of sex-based gene expression followed by validation by qRT-PCR identified that concurrent upregulation of FBN2 and IGF2BP3, and downregulation of TINAGL1 in craniosynostosis cases were all associated with increased RUNX2 expression and may represent a transcriptomic signature that can be used to characterize a subset of single-suture craniosynostosis cases.
%U http://www.la-press.com/unique-sex-based-approach-identifies-transcriptomic-biomarkers-associa-article-a3187