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A Pilot Microarray Study

Yang Tang, MD, PhD; Donald L. Gilbert, MD, MS; Tracy A. Glauser, MD; Andrew D. Hershey, MD, PhD; Frank R. Sharp, MD

Arch Neurol. 2005;62:210-215.

Background  Tissue gene expression profiling with arrays measures the transcription of thousands of genes. However, this approach cannot be readily used to guide clinical neurologic practice.

Objectives  To determine whether clinical neurologic diseases are associated with unique patterns of up- and down-regulated genes in whole blood and to explore the possibility of using peripheral blood as a surrogate tissue in these diseases.

Design  Case-control study.

Setting  University-based pediatric and adult neurology clinics.

Participants  Patients with neurofibromatosis type 1, epilepsy, or Tourette syndrome diagnosed using traditional clinical criteria; controls without disease; and controls with neurologic disease.

Main Outcome Measure  Blood gene expression levels of greater than 12 000 genes, measured using U95A arrays.

Results  Neurofibromatosis type 1 and childhood epilepsy treated with carbamazepine or valproic acid are associated with distinct patterns of blood gene expression. Patients with valproic acid–responsive vs valproic acid–refractory epilepsy formed distinct subclusters. Tourette syndrome was characterized by several gene expression clusters. In 1 cluster, 6 genes—all associated with immune cell function—were overexpressed.

Conclusion  Blood gene expression profiling can provide surrogate markers for neurologic diseases without obvious blood phenotypes.

Author Affiliations: Department of Neurology and Neuroscience Program, University of Cincinnati (Drs Tang and Sharp), and Division of Neurology, Cincinnati Children’s Hospital Medical Center (Drs Gilbert, Glauser, Hershey, and Sharp), Cincinnati, Ohio.

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