Abstracts

Specific genomic profiles have been noted in the blood of patients with various neurological disorders including Down syndrome, Neurofibromatosis, Tuberous Sclerosis, and Tourette syndrome. This study aimed to determine if specific genomic profiles existed in the blood of children with newly diagnosed and untreated idiopathic epilepsy compared to normal children., Patients with untreated idiopathic generalized epilepsy (IGE), untreated idiopathic partial epilepsy (IPE) or healthy children with no history of epilepsy (NML) were enrolled in this IRB approved study. RNA was extracted from whole blood and gene expression was determined using Affymetrix U133 2.0 PLUS microarray chips.
Using microarray expression data, an analysis of variance (ANOVA) model with epilepsy type (IGE v. IPE v. NML), gender and age (where age was dichotomized over the median of 10 years) was used to identify genes (with a 90% confidence of having false discovery rate, FDR [lt] 0.1) that differentiated between the three groups (IGE, IPE and NML). Pairwise comparisons were performed to identify significantly differentiated genes between groups. Gene ontology (GO) analysis was performed on the IGE and IPE groups from the genes that differentiated between the three groups. GO classes and parent classes with at least 5 observations in the selected subset and with an Observed vs. Expected ratio of at least 2 were reported., A total of 79 children were enrolled; 21 with IPE, 30 with IGE and 28 NML patients. After adjustment for age and gender, 460 genes (with a 90% confidence of having FDR [lt] 0.1) were differentially expressed among the epilepsy groups. Pairwise comparisons showed: IGE v. NML had 301 significantly differentiated genes, (overall p = 0.002), IPE v. NML had 308 significantly differentiated genes (overall p=0.003) and IPE v. IGE had 26 significantly differentiated genes (overall p[lt] 0.001). From the 460 genes which differentiated the IGE v. IPE v. NML with FDR [lt] 0.1, two gene ontologies were found in the comparison of IGE v. IPE, where the 61 most significant genes contained no more than 5 false discoveries with 90% confidence. The two gene ontologies were intracellular non-membrane-bound organelle (GO id 0043232) and non-membrane-bound organelle (GO id 0043228) each with Observed vs. Expected ratios of 2.67., Specific genomic profiles exist in children with idiopathic generalized epilepsy and idiopathic partial epilepsy that differentiate from normal controls and from each other. These profiles may provide insight into the underlying process and may represent an additional tool for proper diagnosis and classification of pediatric epilepsy., (Supported by NIH-R21-NS044956.)