Copy number variation in patients with cervical artery dissection

Grond-Ginsbach, Caspar, Chen, Bowang, Pjontek, Rastislav, Wiest, Tina, Jiang, Yanxiang, Burwinkel, Barbara, Tchatchou, Sandrine, Krawczak, Michael, Schreiber, Stefan, Brandt, Tobias, Kloss, Manja, Arnold, Marie-Luise, Hemminki, Kari, Lichy, Christoph, Lyrer, Philippe A., Hausser, Ingrid and Engelter, Stefan T. (2012) Copy number variation in patients with cervical artery dissection European Journal of Human Genetics, 20 (12). pp. 1295-1299.

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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. European Journal of Human Genetics (2012) 20, 1295-1299; doi:10.1038/ejhg.2012.82; published online 23 May 2012

Document Type: Article
Research affiliation: Kiel University
OceanRep > The Future Ocean - Cluster of Excellence
ISSN: 1018-4813
Projects: Future Ocean
Date Deposited: 14 May 2014 10:06
Last Modified: 14 May 2014 10:06

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