title: Genetic Imbalance in Patients with Cervical Artery Dissection.
abstract: BACKGROUND
  Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) =1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107).
  
  
  CONCLUSIONS
  The findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.
authors.affiliation: Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Caspar
authors.initials: C
authors.lastname: Grond-Ginsbach
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen, China.
authors.forename: Bowang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Institute of Medical Informatics and Statistics, Christian-Albrechts University of Kiel, Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.affiliation: Department of Neuroradiology, University of Aachen, Aachen, Germany.
authors.forename: Rastislav
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authors.lastname: Pjontek
authors.affiliation: School of Informatics, University of Edinburgh, United Kingdom.
authors.forename: Philip
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authors.lastname: Ginsbach
authors.affiliation: Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Shérine
authors.initials: S
authors.lastname: Abboud
authors.affiliation: Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Arnold
authors.affiliation: Cerebrovascular Unit IRCCS Foundation C.Besta Neurological Institute, via Celoria 11, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bersano
authors.affiliation: Clinics for Neurologic Rehabilitation, Kliniken Schmieder, Heidelberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Brandt
authors.affiliation: Stroke Unit, Perugia University Hospital, Perugia, Italy.
authors.forename: Valeria
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authors.lastname: Caso
authors.affiliation: Department of Neurology, Hôpital Lariboisière, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Debette
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany;; Munich Cluster of Systems Neurology (SyNergy), Munich Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dichgans
authors.affiliation: Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany.
authors.forename: Andreas
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authors.lastname: Geschwendtner
authors.affiliation: Department of Neurology, Milan, San Raffaele University Hospital, Milan, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Giacalone
authors.affiliation: Department of Neurology, Sanatorio Allende, Cordoba, Argentina.
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Martin
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Metso
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Metso
authors.affiliation: Department of Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany.
authors.forename: Armin J
authors.initials: AJ
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authors.affiliation: Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Manja
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authors.lastname: Kloss
authors.affiliation: Department of Neurology, Klinikum Memmingen, Memmingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichy
authors.affiliation: Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
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authors.lastname: Pezzini
authors.affiliation: Department of Neurology and Stroke Center, Basel University Hospital, Basel, Switzerland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Traenka
authors.affiliation: Department of Internal Medicine, University Hospital Schleswig Holstein, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: Vesalius Research Center, Experimental Neurology - Laboratory of Neurobiology, Leuven, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
authors.affiliation: Paris Descartes University, INSERM UMR S894, Department of Neurology, Sainte-Anne Hospital, Paris, France;; University of Caen Basse Normandie, INSERM U919, Department of Neurology, CHU Côte de Nacre, Caen, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Touzé
authors.affiliation: Department of Recovery and Functional Rehabilitation, IRCCS Don Gnocchi Foundation, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Del Zotto
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland;; Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.affiliation: INSERM U 1171. University hospital of Lille. Department of Neurology. Lille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Leys
authors.affiliation: Department of Neurology and Stroke Center, Basel University Hospital, Basel, Switzerland.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Lyrer
authors.affiliation: Department of Neurology and Stroke Center, Basel University Hospital, Basel, Switzerland;; Neurorehabilitation Unit, University Center for Medicine of Aging and Rehabilitation, Felix Platter-Spital, Basel, Switzerland.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Engelter
keywords: Cardiovascular system development; Cervical artery dissection; Copy number variation; Rare genetic variation