title: Copy number variation in patients with cervical artery dissection.
abstract: Cervical artery dissection (CeAD) occurs in healthy young individuals and often entails ischemic stroke. Skin biopsies from most CeAD-patients show minor connective tissue alterations. We search for rare genetic deletions and duplication that may predispose to CeAD. Forty-nine non-traumatic CeAD-patients with electron microscopic (EM) alterations of their dermal connective tissue (EM+ patients) and 21 patients with normal connective tissue in skin biopsies (EM- patients) were analyzed. Affymetrix 6.0 microarrays (Affymetrix) from all patients were screened for copy number variants (CNVs). CNVs absent from 403 control subjects and from 2402 published disease-free individuals were considered as CeAD-associated. The genetic content of undentified CNVs was analyzed by means of the Gene Ontology (GO) Term Mapper to detect associations with biological processes. In 49 EM+ patients we identified 13 CeAD-associated CNVs harboring 83 protein-coding genes. In 21 EM- patients we found five CeAD-associated CNVs containing only nine genes (comparison of CNV gene density between the groups: Mann-Whitney P=0.039). Patients' CNVs were enriched for genes involved in extracellular matrix organization (COL5A2, COL3A1, SNTA1, P=0.035), collagen fibril organization COL5A2, COL3A1, (P=0.0001) and possibly for genes involved in transforming growth factor beta (TGF)-beta receptor signaling pathway (COL3A1, DUPS22, P=0.068). We conclude that rare genetic variants may contribute to the pathogenesis of CeAD, in particular in patients with a microscopic connective tissue phenotype.
authors.affiliation: Department of Neurology, University of Heidelberg, Heidelberg, Germany. Caspar.Grond-Ginsbach@med.uni-heidelberg.de
authors.forename: Caspar
authors.initials: C
authors.lastname: Grond-Ginsbach
authors.forename: Bowang
authors.initials: B
authors.lastname: Chen
authors.forename: Rastislav
authors.initials: R
authors.lastname: Pjontek
authors.forename: Tina
authors.initials: T
authors.lastname: Wiest
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Sandrine
authors.initials: S
authors.lastname: Tchatchou
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Tobias
authors.initials: T
authors.lastname: Brandt
authors.forename: Manja
authors.initials: M
authors.lastname: Kloss
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Arnold
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichy
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Lyrer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hausser
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Engelter
mesh_terms: D000328:Adult; D020215:Carotid Artery, Internal, Dissection / Q000235:genetics*; D016022:Case-Control Studies; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003238:Connective Tissue / Q000473:pathology; D056915:DNA Copy Number Variations; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D056726:Genetic Association Studies; D056426:Genetic Loci; D006801:Humans; D008297:Male; D015291:Transforming Growth Factors / Q000235:genetics / Q000378:metabolism; D020217:Vertebral Artery Dissection / Q000235:genetics*
chemical_list: D015291:Transforming Growth Factors; D003094:Collagen