Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Feb;27(2):317-324.
doi: 10.1038/s41431-018-0274-4. Epub 2018 Oct 24.

A stroke gene panel for whole-exome sequencing

Andreea Ilinca  1   2 , Sofie Samuelsson  3 , Paul Piccinelli  3 , Maria Soller  3   4 , Ulf Kristoffersson  3 , Arne G Lindgren  5   6
Affiliations

A stroke gene panel for whole-exome sequencing

Andreea Ilinca et al. Eur J Hum Genet. 2019 Feb.

Abstract

Extensive analyses of known monogenic causes of stroke by whole-exome/genome sequencing are technically possible today. We here aimed to compile a comprehensive panel of genes associated with monogenic causes of stroke for use in clinical and research situations. We systematically searched the publically available database Online Mendelian Inheritance in Man, and validated the entries against original peer-reviewed publications in PubMed. First, we selected known pathogenic or putatively pathogenic stroke genes reported in at least one person with stroke, and classified the stroke phenotype for each gene into eight subgroups: (1) large artery atherosclerotic, (2) large artery non-atherosclerotic (tortuosity, dolichoectasia, aneurysm, non-atherosclerotic dissection, occlusion), (3) cerebral small-vessel diseases, (4) cardioembolic (arrhythmia, heart defect, cardiomyopathy), (5) coagulation dysfunctions (venous thrombosis, arterial thrombosis, bleeding tendency), (6) intracerebral hemorrhage, (7) vascular malformations (cavernoma, arteriovenous malformations), and (8) metabolism disorders. Second, we selected other genes that may plausibly cause stroke through diseases related to stroke, but without any documented stroke patient description. A third section comprised SNPs associated with stroke in genome-wide association studies (GWAS). We identified in total 214 genes: 120 associated with stroke, 62 associated with diseases that may cause stroke, and 32 stroke-related genes from recent GWAS. We describe these 214 genes and the clinical stroke subtype(s) associated with each of them. The resulting gene panel can be used to interpret exome sequencing results regarding monogenic stroke. Based on the panel's clinical phenotype description, the pathogenicity of novel variants in these genes may be evaluated in specific situations.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Systematic identification of genes related to monogenic stroke, and inclusion of genes in panels. OMIM = Online Mendelian Inheritance in Man; GWAS = genome-wide association studies, SNP = single-nucleotide polymorphism
See this image and copyright information in PMC

References

    1. Hay SI, Abajobir AA, Abate KH, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1260–344. - PMC - PubMed
    1. Flossmann E, Schulz UG, Rothwell PM. Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke. Stroke. 2004;35:212–27. doi: 10.1161/01.STR.0000107187.84390.AA. - DOI - PubMed
    1. Meschia JF, Brown RD, Jr, Brott TG, et al. Feasibility of an affected sibling pair study in ischemic stroke: results of a 2-center family history registry. Stroke. 2001;32:2939–41. doi: 10.1161/hs1201.099795. - DOI - PubMed
    1. Jood K, Ladenvall C, Rosengren A, et al. Family history in ischemic stroke before 70 years of age: the Sahlgrenska Academy Study on Ischemic Stroke. Stroke. 2005;36:1383–7. doi: 10.1161/01.STR.0000169944.46025.09. - DOI - PubMed
    1. Starby H, Delavaran H, Andsberg G, et al. Multiplicity of risk factors in ischemic stroke patients: relations to age, sex, and subtype—a study of 2,505 patients from the Lund Stroke Register. Neuroepidemiology. 2014;42:161–8. doi: 10.1159/000357150. - DOI - PMC - PubMed

Publication types