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Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
P. Reková, G. Dostálová, D. Kemlink, J. Paulasová Schwabová, Z. Dubská, M. Vaneckova, M. Mašek, O. Kodet, H. Poupětová, S. Mazurová, A. Rajdova, E. Vlckova, A. Táboříková, Š. Fafejtová, M. Nevsimalova, A. Linhart, A. Tomek
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
MZCZ-DRO-VFN64165
Ministerstvo Zdravotnictví Ceské Republiky
NLK
Free Medical Journals
od 2012
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2019-01-01
Open Access Digital Library
od 2012-01-01
Open Access Digital Library
od 2012-01-01
Health & Medicine (ProQuest)
od 2019-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2012
PubMed
34441839
DOI
10.3390/jcm10163543
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
Fabry disease (FD) is a rare X-linked disorder of glycosphingolipid metabolism caused by pathogenic variants within the alpha-galactosidase A (GLA) gene, often leading to neurological manifestations including stroke. Multiple screening programs seeking GLA variants among stroke survivors lacked detailed phenotype description, making the interpretation of the detected variant's pathogenicity difficult. Here, we describe detailed clinical characteristics of GLA variant carriers identified by a nationwide stroke screening program in the Czech Republic. A total of 23 individuals with 8 different GLA variants were included in the study. A comprehensive diagnostic workup was performed by a team of FD specialists. The investigation led to the suggestion of phenotype reclassification for the G325S mutation from late-onset to classical. A novel variant R30K was found and was classified as a variant of unknown significance (VUS). The typical manifestation in our FD patients was a stroke occurring in the posterior circulation with an accompanying pathological finding in the cerebrospinal fluid. Moreover, we confirmed that cornea verticillata is typically associated with classical variants. Our findings underline the importance of detailed phenotype description and data sharing in the correct identification of pathogenicity of gene variants detected by high-risk-population screening programs.
Department of Neurology and Stroke Centre Country Hospital Chomutov 430 12 Chomutov Czech Republic
Department of Neurology and Stroke Centre Hospital Karlovy Vary 360 01 Karlovy Vary Czech Republic
Department of Neurology Hospital Ceske Budejovice 370 01 České Budějovice Czech Republic
Institute of Anatomy 1st Faculty of Medicine Charles University Prague 128 08 Prague Czech Republic
Citace poskytuje Crossref.org
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- $a Reková, Petra $u Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic
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- $a Fabry disease (FD) is a rare X-linked disorder of glycosphingolipid metabolism caused by pathogenic variants within the alpha-galactosidase A (GLA) gene, often leading to neurological manifestations including stroke. Multiple screening programs seeking GLA variants among stroke survivors lacked detailed phenotype description, making the interpretation of the detected variant's pathogenicity difficult. Here, we describe detailed clinical characteristics of GLA variant carriers identified by a nationwide stroke screening program in the Czech Republic. A total of 23 individuals with 8 different GLA variants were included in the study. A comprehensive diagnostic workup was performed by a team of FD specialists. The investigation led to the suggestion of phenotype reclassification for the G325S mutation from late-onset to classical. A novel variant R30K was found and was classified as a variant of unknown significance (VUS). The typical manifestation in our FD patients was a stroke occurring in the posterior circulation with an accompanying pathological finding in the cerebrospinal fluid. Moreover, we confirmed that cornea verticillata is typically associated with classical variants. Our findings underline the importance of detailed phenotype description and data sharing in the correct identification of pathogenicity of gene variants detected by high-risk-population screening programs.
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