Copy number variation in patients with cervical artery dissection

• Verfasst von: Grond-Ginsbach, Caspar [VerfasserIn]
• Verfasst von: Pjontek, Rastislav [VerfasserIn]
• Verfasst von: Wiest, Tina [VerfasserIn]
• Verfasst von: Burwinkel, Barbara [VerfasserIn]
• Verfasst von: Kloss, Manja [VerfasserIn]
• Verfasst von: Arnold, Marie-Luise [VerfasserIn]
• Verfasst von: Lichy, Christoph [VerfasserIn]
• Verfasst von: Haußer-Siller, Ingrid [VerfasserIn]
• Titel: Copy number variation in patients with cervical artery dissection
• Verf.angabe: Caspar Grond-Ginsbach, Bowang Chen, Rastislav Pjontek, Tina Wiest, Yanxiang Jiang, Barbara Burwinkel, Sandrine Tchatchou, Michael Krawczak, Stefan Schreiber, Tobias Brandt, Manja Kloss, Marie-Luise Arnold, Kari Hemminki, Christoph Lichy, Philippe A. Lyrer, Ingrid Hausser, Stefan T. Engelter
• E-Jahr: 2012
• Jahr: 23 May 2012
• Umfang: 5 S.
• Teil: volume:20
• Teil: year:2012
• Teil: number:12
• Teil: pages:1295-1299
• Teil: extent:5
• Fussnoten: Gesehen am 29.05.2019
• Titel Quelle: Enthalten in: European journal of human genetics
• Ort Quelle: Basingstoke : Stockton Press, 1998
• Jahr Quelle: 2012
• Band/Heft Quelle: 20(2012), 12, Seite 1295-1299
• ISSN Quelle: 1476-5438
• DOI: doi:10.1038/ejhg.2012.82
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1575824124

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.