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Stroke Genetics pp 247–262Cite as

Genetics of Cervical Artery Dissection

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Abstract

Despite being relatively rare in the general population, cervical artery dissection (CeAD) is a major cause of ischemic stroke in young and middle-aged adults. Its risk factors and underlying mechanisms are poorly understood. Seldom, CeAD can be caused by a monogenic connective tissue disease, mainly vascular Ehlers-Danlos syndrome. In the absence of a known monogenic connective tissue disorder, a small proportion of CeAD patients (<3%) have a family history of symptomatic CeAD and in some series about half of CeAD patients were shown to have skin connective tissue abnormalities segregating in families according to an autosomal dominant pattern. A few linkage studies were performed that have so far yielded negative results. In the majority of CeAD cases, a number of arguments suggest that genetic factors might play a role as part of a multifactorial predisposition. Several candidate gene association studies have been published, on relatively small samples, which did not reveal any robust associations. Recently, the first genome-wide association study (GWAS) of CeAD was published, resulting from a large international effort gathering samples from over 2000 CeAD patients. This GWAS identified a common intronic variant in PHACTR1 to be significantly associated with CeAD risk. Interestingly, the same variant has also shown association with migraine, fibromuscular dysplasia, and myocardial infarction, with effects in the opposite direction for the latter. Additional studies on larger samples, including the analysis of rare variants, are required to further reveal the genetic underpinnings of CeAD.

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  1. InsermU1219, Bordeaux University, 146 rue Léo Saignat, 33076, Bordeaux, France

    Stéphanie Debette M.D., Ph.D.

  2. Department of Neurology, Bordeaux University Hospital, Institute for Neurodegenerative Disease, Bordeaux, France

    Stéphanie Debette M.D., Ph.D.

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  1. Stéphanie Debette M.D., Ph.D.
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  1. Department of Neurology, Institute of Cardiovascular Research Royal Holloway College, University of London Imperial College London Healthcare NHS Trust, London, United Kingdom

    Pankaj Sharma

  2. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA

    James F. Meschia

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Debette, S. (2017). Genetics of Cervical Artery Dissection. In: Sharma, P., Meschia, J. (eds) Stroke Genetics. Springer, Cham. https://doi.org/10.1007/978-3-319-56210-0_13

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