Sauvigny, Thomas, Alawi, Malik, Krause, Linda ORCID: 0000-0002-8490-5717, Renner, Sina, Spohn, Michael, Busch, Alice, Kolbe, Verena, Altmueller, Janine, Loescher, Britt-Sabina, Franke, Andre, Brockmann, Christian, Lieb, Wolfgang, Westphal, Manfred, Schmidt, Nils Ole ORCID: 0000-0001-6910-8843, Regelsberger, Jan and Rosenberger, Georg (2020). Exome sequencing in 38 patients with intracranial aneurysms and subarachnoid hemorrhage. J. Neurol., 267 (9). S. 2533 - 2546. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1432-1459

Full text not available from this repository.

Abstract

Objective Genetic risk factors for unruptured intracranial aneurysms (UIA) and aneurysmal subarachnoid hemorrhage (aSAH) are poorly understood. We aimed to verify recently reported risk genes and to identify novel sequence variants involved in the etiology of UIA/aSAH. Methods We performed exome sequencing (ES) in 35 unrelated individuals and 3 family members, each with a history of UIA and/or aSAH. We searched for sequence variants with minor allele frequency (MAF) <= 5% in the reported risk genes ADAMTS15, ANGPTL6, ARHGEF17, LOXL2, PCNT, RNF213, THSD1 and TMEM132B. To identify novel putative risk genes we looked for unknown (MAF = 0) variants shared by the three relatives. Results We identified 20 variants with MAF <= 5% in 18 individuals: 9 variants in PCNT (9 patients), 4 in RNF213 (3 patients), 3 in THSD1 (6 patients), 2 in ANGPTL6 (3 patients), 1 in ADAMTS15 (1 patient) and 1 in TMEM132B (1 patient). In the affected family, prioritization of shared sequence variants yielded five novel putative risk genes. Based on predicted pathogenicity of identified variants, population genetics data and a high functional relevance for vascular biology, EDIL3 was selected as top candidate and screened in additional 37 individuals with UIA and/or aSAH: a further very rare EDIL3 sequence variant in two unrelated sporadic patients was identified. Conclusions Our data support a role of sequence variants in PCNT, RNF213 and THSD1 as susceptibility factors for cerebrovascular disease. The documented function in vascular wall integrity, the crucial localization of affected amino acids and gene/variant association tests suggest EDIL3 as a further valid candidate disease gene for UIA/aSAH.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Sauvigny, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alawi, MalikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krause, LindaUNSPECIFIEDorcid.org/0000-0002-8490-5717UNSPECIFIED
Renner, SinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spohn, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busch, AliceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolbe, VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loescher, Britt-SabinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brockmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lieb, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westphal, ManfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Nils OleUNSPECIFIEDorcid.org/0000-0001-6910-8843UNSPECIFIED
Regelsberger, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenberger, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-334489
DOI: 10.1007/s00415-020-09865-6
Journal or Publication Title: J. Neurol.
Volume: 267
Number: 9
Page Range: S. 2533 - 2546
Date: 2020
Publisher: SPRINGER HEIDELBERG
Place of Publication: HEIDELBERG
ISSN: 1432-1459
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DEVELOPMENTAL ENDOTHELIAL LOCUS-1; POPULATION; VARIANTS; RARE; ASSOCIATION; PREVALENCE; GENETICS; PROTEIN; GROWTH; MUTATIONMultiple languages
Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33448

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item