A subgroup of Tourette's patients overexpress specific natural killer cell genes in blood: a preliminary report.
Gilles de la Tourette Syndrome (TS) is a heritable, neurodevelopmental disorder characterized by motor and vocal tics. As no single gene or region has emerged from standard linkage approaches, TS may result from several as-yet-unidentified genetic factors, and may also occur due to infection-triggered, autoimmune processes. Etiological or pathogenic differences might result in clinically indistinguishable TS subgroups. We have previously used whole genome human oligonucleotide microarrays in an attempt to identify patterns of gene expression in blood linked with TS. In this proof-of-principle study, we applied Principal Components Analysis to a previously collected set of 16 familial TS and 16 control blood samples to identify subgroups. Fourteen genes, primarily Natural Killer Cell (NK) genes, discriminated between TS and all controls. Granzyme B and NKG7 were confirmed using RT-PCR. Five probesets (four genes) reside in chromosomal regions previously linked to familial TS or obsessive-compulsive disorder. Using the 14 genes, a Principal Components Analysis as well as a cluster analysis identified a TS subgroup (n = 10/16) that overexpressed the NK genes. 7/10 subjects within this subgroup were diagnosed with attention-deficit hyperactivity disorder (ADHD), suggesting that this expression profile might be associated with TS and co-morbid ADHD. Principal Components Analysis of gene expression in blood may be useful for identifying subgroups of other complex neurodevelopmental diseases, and the gene expression profile identified in this study may provide a biomarker for at least one subgroup of heritable TS.
Lit
Lisa
L
Genetics Graduate Group, Department of Neurology, M.I.N.D. Institute, University of California at Davis, Sacramento, CA 95817, USA. Llit@ucdavis.edu
Gilbert
Donald L
DL
Walker
Wynn
W
Sharp
Frank R
FR
D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D053804:Granzymes / Q000097:blood / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000097:blood; D005879:Tourette Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*
D015415:Biomarkers; D008565:Membrane Proteins; C499363:NKG7 protein, human; D012333:RNA, Messenger; D053804:Granzymes