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
Review
. 2015 Dec;262(12):2601-16.
doi: 10.1007/s00415-015-7794-4. Epub 2015 Jun 3.

Monogenic causes of stroke: now and the future

Rhea Y Y Tan  1 , Hugh S Markus  2
Affiliations
Review

Monogenic causes of stroke: now and the future

Rhea Y Y Tan et al. J Neurol. 2015 Dec.

Abstract

Most stroke is multifactorial with multiple polygenic risk factors each conferring small increases in risk interacting with environmental risk factors, but it can also arise from mutations in a single gene. This review covers single-gene disorders which lead to stroke as a major phenotype, with a focus on those which cause cerebral small vessel disease (SVD), an area where there has been significant recent progress with findings that may inform us about the pathogenesis of SVD more broadly. We also discuss the impact that next generation sequencing technology (NGST) is likely to have on clinical practice in this area. The most common form of monogenic SVD is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, due to the mutations in the NOTCH3 gene. Several other inherited forms of SVD include cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, retinal vasculopathy with cerebral leukodystrophy, collagen type IV α1 and α2 gene-related arteriopathy and FOXC1 deletion related arteriopathy. These monogenic forms of SVD, with overlapping clinical phenotypes, are beginning to provide insights into how the small arteries in the brain can be damaged and some of the mechanisms identified may also be relevant to more common sporadic SVD. Despite the discovery of these disorders, it is often challenging to clinically and radiologically distinguish between syndromes, while screening multiple genes for causative mutations that can be costly and time-consuming. The rapidly falling cost of NGST may allow quicker diagnosis of these rare causes of SVD, and can also identify previously unknown disease-causing variants.

Keywords: CADASIL; CARASIL; COL4A1; Genetics; Next generation sequencing; Retinal vasculopathy with cerebral leukodystrophy; Small vessel disease; Stroke.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Genetic Insights into Cerebrovascular Disorders: A Comprehensive Review.
    Al-Mufti F, Alkanaq A, Amuluru K, Nuoman R, Abdulrazzaq A, Sami T, Nuoaman H, Hayes-Rosen C, Prestigiacomo CJ, Gandhi CD. Al-Mufti F, et al. J Vasc Interv Neurol. 2017 Oct;9(5):21-32. J Vasc Interv Neurol. 2017. PMID: 29163746 Free PMC article. No abstract available.
  • Nucleic Acid Therapies for Ischemic Stroke.
    Henninger N, Mayasi Y. Henninger N, et al. Neurotherapeutics. 2019 Apr;16(2):299-313. doi: 10.1007/s13311-019-00710-x. Neurotherapeutics. 2019. PMID: 30635869 Free PMC article. Review.
  • Genetic variation at 16q24.2 is associated with small vessel stroke.
    Traylor M, Malik R, Nalls MA, Cotlarciuc I, Radmanesh F, Thorleifsson G, Hanscombe KB, Langefeld C, Saleheen D, Rost NS, Yet I, Spector TD, Bell JT, Hannon E, Mill J, Chauhan G, Debette S, Bis JC, Longstreth WT Jr, Ikram MA, Launer LJ, Seshadri S; METASTROKE, UK Young Lacunar DNA Study, NINDS Stroke Genetics Network, Neurology Working Group of the CHARGE Consortium; Hamilton-Bruce MA, Jimenez-Conde J, Cole JW, Schmidt R, Słowik A, Lemmens R, Lindgren A, Melander O, Grewal RP, Sacco RL, Rundek T, Rexrode K, Arnett DK, Johnson JA, Benavente OR, Wasssertheil-Smoller S, Lee JM, Pulit SL, Wong Q, Rich SS, de Bakker PI, McArdle PF, Woo D, Anderson CD, Xu H, Heitsch L, Fornage M, Jern C, Stefansson K, Thorsteinsdottir U, Gretarsdottir S, Lewis CM, Sharma P, Sudlow CL, Rothwell PM, Boncoraglio GB, Thijs V, Levi C, Meschia JF, Rosand J, Kittner SJ, Mitchell BD, Dichgans M, Worrall BB, Markus HS; International Stroke Genetics Consortium. Traylor M, et al. Ann Neurol. 2017 Mar;81(3):383-394. doi: 10.1002/ana.24840. Ann Neurol. 2017. PMID: 27997041 Free PMC article.
  • Migraine and stroke.
    Zhang Y, Parikh A, Qian S. Zhang Y, et al. Stroke Vasc Neurol. 2017 May 29;2(3):160-167. doi: 10.1136/svn-2017-000077. eCollection 2017 Sep. Stroke Vasc Neurol. 2017. PMID: 28989805 Free PMC article. Review.
  • Loss of the serine protease HTRA1 impairs smooth muscle cells maturation.
    Klose R, Prinz A, Tetzlaff F, Weis EM, Moll I, Rodriguez-Vita J, Oka C, Korff T, Fischer A. Klose R, et al. Sci Rep. 2019 Dec 3;9(1):18224. doi: 10.1038/s41598-019-54807-6. Sci Rep. 2019. PMID: 31796853 Free PMC article.
See all "Cited by" articles

References

    1. Acta Neurol Scand. 2015 Jan;131(1):30-6 - PubMed
    1. Neurology. 2015 Mar 3;84(9):918-26 - PubMed
    1. Neurology. 2002 Mar 12;58(5):817-20 - PubMed
    1. Neurology. 2014 Sep 9;83(11):1029-31 - PubMed
    1. Neuropathology. 2003 Dec;23(4):327-34 - PubMed

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources