Gene expression analysis in untreated absence epilepsy demonstrates an inconsistent pattern.
Childhood and Juvenile Absence Epilepsy account for 30% of all genetic generalized epilepsies with a strong genetic contribution. At the current state the genetic background remains to be resolved. The aim of this study was to identify disease associated transcripts pinpointing potential underlying disease mechanisms in patients with CAE and JAE.



We performed gene expression analysis from peripheral blood mononuclear cells (PBMCs) in 30 patients with newly-diagnosed absence epilepsy prior to initiating treatment and 30 healthy age - and gender-matched pediatric controls. In a first group (group 1), 10 patients and controls we performed genome-wide transcriptome analysis using the Affymetrix HG U133 2.0+ microarray. 75 differentially expressed genes were followed up by qRT-PCR in two independent groups of 10 patients and controls (group 2 and 3). Furthermore, we analyzed 18 candidate genes by qRT-PCR in groups 2 and 3, which had previously been considered strong candidates for genetic epilepsies.



Genome-wide gene expression analysis in group 1 revealed 601 differentially regulated genes. Independent validation of 75 group 1-derived genes by qRT-PCR in groups 2 and 3 confirmed candidate genes with a consistent, but non-significant pattern of up- or down-regulation across all groups (ATP1B3, CAND1, PRPF6, TRIM8). Previously known genes including GABRA1, GABRB3, GABRG2, and RCN2 showed evidence for up- or down-regulation in individual experiments, but were not reliable across groups either.



Gene expression analysis in absence epilepsy from PMBCs displayed a high degree of heterogeneity between different patient groups. Our study provides several potentially interesting candidate genes, while demonstrating the limits of using gene expression analysis from blood in the identification of novel pathogenic mechanisms. In particular, we found that gene expression levels vary in response to altered experimental conditions, representing a substantial challenge for the identification of disease-related gene expression signatures for neurological diseases from whole blood.
Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany. Electronic address: m.v.deimling@pedneuro.uni-kiel.de.
Markus
M
von Deimling
Institute of Clinical Molecular Biology, Kiel University, Kiel, Schleswig-Holstein, Germany. Electronic address: r.haesler@mucosa.de.
Robert
R
Häsler
Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany. Electronic address: vvolz@hotmail.de.
Verena
V
Steinbach
Department of Pediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany. Electronic address: holterhus@pediatrics.uni-kiel.de.
Paul-Martin
PM
Holterhus
Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany; Northern German Epilepsy Center for Children and Adolescents, Schwentinental-Raisdorf, Schleswig-Holstein, Germany. Electronic address: s.vonspiczak@pedneuro.uni-kiel.de.
Sarah
S
von Spiczak
Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany; Northern German Epilepsy Center for Children and Adolescents, Schwentinental-Raisdorf, Schleswig-Holstein, Germany. Electronic address: stephani@pedneuro.uni-kiel.de.
Ulrich
U
Stephani
Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany; Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: helbigi@email.chop.edu.
Ingo
I
Helbig
Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany. Electronic address: muhle@pedneuro.uni-kiel.de.
Hiltrud
H
Muhle
D015536:Down-Regulation; D004832:Epilepsy, Absence / Q000097:blood* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male
Absence epilepsy; CAE; GGE; Gene expression