Cryptogenic stroke and small fiber neuropathy of unknown etiology in patients with alpha-galactosidase A -10T genotype

Background: Fabry disease (FD) is a multisystemic disorder with typical neurological manifestations such as stroke and small fiber neuropathy (SFN), caused by mutations of the alpha-galactosidase A (GLA) gene. We analyzed 15 patients carrying the GLA haplotype -10C>T [rs2071225], IVS2-81_-77delCA...

Authors: Schelleckes, Michael
Lenders, Malte
Guske, Katrin
Schmitz, Boris
Tanislav, Christian
Ständer, Sonja
Metze, Dieter
Katona, István
Weis, Joachim
Brand, Stefan-Martin
Duning, Thomas
Brand, Eva
Division/Institute:FB 13: Biologie
FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2014
Date of publication on miami:08.01.2015
Modification date:10.07.2019
Edition statement:[Electronic ed.]
Source:Orphanet Journal of Rare Diseases 9 (2014) 178, 1-13
Subjects:Neuropathic pain; Stroke; Cerebrovascular disease; Fabry disease; Gene expression regulation
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:1750-1172
URN:urn:nbn:de:hbz:6-00399363714
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-00399363714
Other Identifiers:DOI: doi:10.1186/s13023-014-0178-5
Digital documents:s13023-014-0178-5.pdf

Background: Fabry disease (FD) is a multisystemic disorder with typical neurological manifestations such as stroke and small fiber neuropathy (SFN), caused by mutations of the alpha-galactosidase A (GLA) gene. We analyzed 15 patients carrying the GLA haplotype -10C>T [rs2071225], IVS2-81_-77delCAGCC [rs5903184], IVS4-16A>G [rs2071397], and IVS6-22C>T [rs2071228] for potential neurological manifestations. Methods and results: Patients were retrospectively analyzed for stroke, transient ischemic attack (TIA), white matter lesions (WML) and SFN with neuropathic pain. Functional impact of the haplotype was determined by molecular genetic methods including real-time PCR, exon trapping, promoter deletion constructs and electrophoretic mobility shift assays. Symptomatic -10T allele carriers suffered from stroke, TIA, WML, and SFN with neuropathic pain. Patients’ mean GLA mRNA expression level was reduced to ~70% (p