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Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic

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 deta...

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Autores principales: Reková, Petra, Dostálová, Gabriela, Kemlink, David, Paulasová Schwabová, Jaroslava, Dubská, Zora, Vaneckova, Manuela, Mašek, Martin, Kodet, Ondřej, Poupětová, Helena, Mazurová, Stella, Rajdova, Aneta, Vlckova, Eva, Táboříková, Alena, Fafejtová, Štěpánka, Nevsimalova, Miroslava, Linhart, Aleš, Tomek, Aleš
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396867/
https://www.ncbi.nlm.nih.gov/pubmed/34441839
http://dx.doi.org/10.3390/jcm10163543
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author Reková, Petra
Dostálová, Gabriela
Kemlink, David
Paulasová Schwabová, Jaroslava
Dubská, Zora
Vaneckova, Manuela
Mašek, Martin
Kodet, Ondřej
Poupětová, Helena
Mazurová, Stella
Rajdova, Aneta
Vlckova, Eva
Táboříková, Alena
Fafejtová, Štěpánka
Nevsimalova, Miroslava
Linhart, Aleš
Tomek, Aleš
author_facet Reková, Petra
Dostálová, Gabriela
Kemlink, David
Paulasová Schwabová, Jaroslava
Dubská, Zora
Vaneckova, Manuela
Mašek, Martin
Kodet, Ondřej
Poupětová, Helena
Mazurová, Stella
Rajdova, Aneta
Vlckova, Eva
Táboříková, Alena
Fafejtová, Štěpánka
Nevsimalova, Miroslava
Linhart, Aleš
Tomek, Aleš
author_sort Reková, Petra
collection PubMed
description 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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spelling pubmed-83968672021-08-28 Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic Reková, Petra Dostálová, Gabriela Kemlink, David Paulasová Schwabová, Jaroslava Dubská, Zora Vaneckova, Manuela Mašek, Martin Kodet, Ondřej Poupětová, Helena Mazurová, Stella Rajdova, Aneta Vlckova, Eva Táboříková, Alena Fafejtová, Štěpánka Nevsimalova, Miroslava Linhart, Aleš Tomek, Aleš J Clin Med Article 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. MDPI 2021-08-12 /pmc/articles/PMC8396867/ /pubmed/34441839 http://dx.doi.org/10.3390/jcm10163543 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Reková, Petra
Dostálová, Gabriela
Kemlink, David
Paulasová Schwabová, Jaroslava
Dubská, Zora
Vaneckova, Manuela
Mašek, Martin
Kodet, Ondřej
Poupětová, Helena
Mazurová, Stella
Rajdova, Aneta
Vlckova, Eva
Táboříková, Alena
Fafejtová, Štěpánka
Nevsimalova, Miroslava
Linhart, Aleš
Tomek, Aleš
Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
title Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
title_full Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
title_fullStr Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
title_full_unstemmed Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
title_short Detailed Phenotype of GLA Variants Identified by the Nationwide Neurological Screening of Stroke Patients in the Czech Republic
title_sort detailed phenotype of gla variants identified by the nationwide neurological screening of stroke patients in the czech republic
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396867/
https://www.ncbi.nlm.nih.gov/pubmed/34441839
http://dx.doi.org/10.3390/jcm10163543
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