Genetic Imbalance in Patients with Cervical Artery Dissection

Caspar Grond-Ginsbach¹, Bowang Chen², Michael Krawczak³, Rastislav Pjontek⁴, Philip Ginsbach⁵, Yanxiang Jiang⁶, Shérine Abboud⁷, Marie-Luise Arnold¹, Anna Bersano⁸, Tobias Brandt⁹, Valeria Caso¹⁰, Stéphanie Debette¹¹, Martin Dichgans¹², Andreas Geschwendtner¹³, Giacomo Giacalone¹⁴, Juan-José Martin¹⁵, Antti J Metso¹⁶, Tiina M Metso¹⁶, Armin J Grau¹⁷, Manja Kloss¹, Christoph Lichy¹⁸, Alessandro Pezzini¹⁹, Christopher Traenka²⁰, Stefan Schreiber²¹, Vincent Thijs²², Emmanuel Touzé²³, Elisabetta Del Zotto²⁴, Turgut Tatlisumak²⁵, Didier Leys²⁶, Philippe A Lyrer²⁰, Stefan T Engelter²⁷; CADISP group.

Affiliations

¹ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
² Department of Biology, South University of Science and Technology of China, Shenzhen, China.
³ Institute of Medical Informatics and Statistics, Christian-Albrechts University of Kiel, Kiel, Germany.
⁴ Department of Neuroradiology, University of Aachen, Aachen, Germany.
⁵ School of Informatics, University of Edinburgh, United Kingdom.
⁶ Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
⁷ Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.
⁸ Cerebrovascular Unit IRCCS Foundation C.Besta Neurological Institute, via Celoria 11, Milan, Italy.
⁹ Clinics for Neurologic Rehabilitation, Kliniken Schmieder, Heidelberg, Germany.
¹⁰ Stroke Unit, Perugia University Hospital, Perugia, Italy.
¹¹ Department of Neurology, Hôpital Lariboisière, Paris, France.
¹² Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany;; Munich Cluster of Systems Neurology (SyNergy), Munich Germany.
¹³ Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany.
¹⁴ Department of Neurology, Milan, San Raffaele University Hospital, Milan, Italy.
¹⁵ Department of Neurology, Sanatorio Allende, Cordoba, Argentina.
¹⁶ Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
¹⁷ Department of Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany.
¹⁸ Department of Neurology, Klinikum Memmingen, Memmingen, Germany.
¹⁹ Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.
²⁰ Department of Neurology and Stroke Center, Basel University Hospital, Basel, Switzerland.
²¹ Department of Internal Medicine, University Hospital Schleswig Holstein, Kiel, Germany.
²² Vesalius Research Center, Experimental Neurology - Laboratory of Neurobiology, Leuven, Belgium.
²³ 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.
²⁴ Department of Recovery and Functional Rehabilitation, IRCCS Don Gnocchi Foundation, Milan, Italy.
²⁵ 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.
²⁶ INSERM U 1171. University hospital of Lille. Department of Neurology. Lille, France.
²⁷ 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.

PMID: 28367076
PMCID: PMC5345335
DOI: 10.2174/1389202917666160805152627

Genetic Imbalance in Patients with Cervical Artery Dissection

Caspar Grond-Ginsbach et al. Curr Genomics. 2017 Apr.

. 2017 Apr;18(2):206-213.

doi: 10.2174/1389202917666160805152627.

Authors

Affiliations

¹ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
² Department of Biology, South University of Science and Technology of China, Shenzhen, China.
³ Institute of Medical Informatics and Statistics, Christian-Albrechts University of Kiel, Kiel, Germany.
⁴ Department of Neuroradiology, University of Aachen, Aachen, Germany.
⁵ School of Informatics, University of Edinburgh, United Kingdom.
⁶ Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany.
⁷ Laboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium.
⁸ Cerebrovascular Unit IRCCS Foundation C.Besta Neurological Institute, via Celoria 11, Milan, Italy.
⁹ Clinics for Neurologic Rehabilitation, Kliniken Schmieder, Heidelberg, Germany.
¹⁰ Stroke Unit, Perugia University Hospital, Perugia, Italy.
¹¹ Department of Neurology, Hôpital Lariboisière, Paris, France.
¹² Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany;; Munich Cluster of Systems Neurology (SyNergy), Munich Germany.
¹³ Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilians Universität, Munich, Germany.
¹⁴ Department of Neurology, Milan, San Raffaele University Hospital, Milan, Italy.
¹⁵ Department of Neurology, Sanatorio Allende, Cordoba, Argentina.
¹⁶ Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
¹⁷ Department of Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany.
¹⁸ Department of Neurology, Klinikum Memmingen, Memmingen, Germany.
¹⁹ Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.
²⁰ Department of Neurology and Stroke Center, Basel University Hospital, Basel, Switzerland.
²¹ Department of Internal Medicine, University Hospital Schleswig Holstein, Kiel, Germany.
²² Vesalius Research Center, Experimental Neurology - Laboratory of Neurobiology, Leuven, Belgium.
²³ 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.
²⁴ Department of Recovery and Functional Rehabilitation, IRCCS Don Gnocchi Foundation, Milan, Italy.
²⁵ 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.
²⁶ INSERM U 1171. University hospital of Lille. Department of Neurology. Lille, France.
²⁷ 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.

PMID: 28367076
PMCID: PMC5345335
DOI: 10.2174/1389202917666160805152627

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).

Conclusion: 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.

Keywords: Cardiovascular system development; Cervical artery dissection; Copy number variation; Rare genetic variation.

PubMed Disclaimer

Figures

**Fig. (1)**
Flow chart of study design.

See this image and copyright information in PMC

References

1. Mikhail F.M. Copy number variations and human genetic disease. Curr. Opin. Pediatr. 2014;26:646–652. - PubMed
1. Almal S.H., Padh H. Implications of gene copy-number variation in health and diseases. J. Hum. Genet. 2012;57:6–13. - PubMed
1. Stankiewicz P., Lupski J.R. Structural variation in the human genome and its role in disease. Annu. Rev. Med. 2010;61:437–455. - PubMed
1. Kuang S.Q., Guo D.C., Prakash S.K., McDonald M.L., Johnson R.J., Wang M., Regalado E.S., Russell L., Cao J.M., Kwartler C., Fraivillig K., Coselli J.S., Safi H.J., Estrera A.L., Leal S.M., LeMaire S.A., Belmont J.W., Milewicz D.M. GenTAC Investigators. Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections. PLoS Genet. 2011;7:e1002118. - PMC - PubMed
1. Soemedi R., Wilson I.J., Bentham J., Darlay R., Töpf A., Zelenika D., Cosgrove C., Setchfield K., Thornborough C., Granados-Riveron J., Blue G.M., Breckpot J., Hellens S., Zwolinkski S., Glen E., Mamasoula C., Rahman T.J., Hall D., Rauch A., Devriendt K., Gewillig M. O', Sullivan, J.; Winlaw, DS.; Bu'Lock, F.; Brook, JD.; Bhattacharya, S.; Lathrop, M.; Santibanez-Koref, M.; Cordell, H.J.; Goodship, J.A.; Keavney, B.D. Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease. Am. J. Hum. Genet. 2012;91:489–501. - PMC - PubMed

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Genetic Imbalance in Patients with Cervical Artery Dissection

Affiliations

Genetic Imbalance in Patients with Cervical Artery Dissection

Authors

Affiliations

Abstract

Figures

References

LinkOut - more resources

Full Text Sources

Other Literature Sources