Detailed phenotype of GLA variants identified by the nationwide neurological screening of stroke patients in the Czech Republic

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10430123" target="_blank" >RIV/00216208:11110/21:10430123 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/21:00074734 RIV/00064203:_____/21:10430123 RIV/00064165:_____/21:10430123 RIV/00216208:11130/21:10430123 RIV/00216224:14110/21:00123211

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=98NNB0z8oG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=98NNB0z8oG</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/jcm10163543" target="_blank" >10.3390/jcm10163543</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Detailed phenotype of GLA variants identified by the nationwide neurological screening of stroke patients in the Czech Republic

Popis výsledku v původním jazyce

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&apos;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.

Název v anglickém jazyce

Detailed phenotype of GLA variants identified by the nationwide neurological screening of stroke patients in the Czech Republic

Popis výsledku anglicky

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&apos;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Clinical Medicine [online]

ISSN

2077-0383

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

17

Strana od-do

3543

Kód UT WoS článku

000690449900001

EID výsledku v databázi Scopus

2-s2.0-85112153199