Czech nationwide screening for Fabry disease in patients on maintenance dialysis: a call for evaluation of population-enriched GLA gene variants of uncertain significance

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10499272" target="_blank" >RIV/00179906:_____/25:10499272 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/25:10499272 RIV/00216208:11120/25:43928600 RIV/00216208:11130/25:10499272 RIV/00216208:11150/25:10499272 and 5 more

Result on the web

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/ckj/sfaf167" target="_blank" >10.1093/ckj/sfaf167</a>

Result language

angličtina

Original language name

Czech nationwide screening for Fabry disease in patients on maintenance dialysis: a call for evaluation of population-enriched GLA gene variants of uncertain significance

Original language description

Background. Fabry disease (FD) is a rare disorder caused by variants in the GLA gene encoding alpha-galactosidase A (GALA), leading to end-stage kidney disease (ESKD), among other health issues. The 2002 Czech nationwide FD screening in ESKD found undiagnosed cases in dialysis patients by examining GALA activity in dried blood spots (DBS). Methods. The second nationwide FD screening (2016-2018; 21-month study) in ESKD patients on maintenance dialysis therapy (MDT) included 112 Czech dialysis units to assess country-wide FD diagnostic guidelines&apos; efficacy in reducing its underdiagnosis. This involved GALA activity and/or lyso-Gb3 levels with GLA sequencing in positive males, the latter applied first in all females, followed by lyso-Gb3 examination in variant-positive cases. Screening-positive cases were referred to the FD center for follow-up and in vitro studies. Results. The 6352 screened cases represent 93.9% of all MDT patients within the study duration. Eight GLA variants were identified in 39 patients, of which seven were in 35 ESKD cases classified as likely benign (LB), with normal lyso-Gb3 levels in all subjects. Four patients (three males with reduced GALA activity and one sequencing-positive female) bear a &quot;hot variant of uncertain significance&quot; (VUS) c.1181T&gt;C(p.Leu394Pro), significantly enriched compared to the general population, suggesting its association with FD. Conclusions. This is one of the largest FD screening schemes in a European ESKD cohort. Subsequent in vitro studies proved that the hot VUS is linked to alternative FD pathogenesis, thereby substantiating the utility of combining biomarkers and sequencing/bioinformatics in FD screening. The broad application of FD diagnostic guidelines has reduced its underdiagnosis in ESKD.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30217 - Urology and nephrology

Project

<a href="/en/project/EF16_026%2F0008448" target="_blank" >EF16_026/0008448: Analysis of Czech Genomes for Theranostics</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Clinical Kidney Journal

ISSN

2048-8505

e-ISSN

2048-8513

Volume of the periodical

18

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

sfaf167

UT code for WoS article

001518589600001

EID of the result in the Scopus database

2-s2.0-105009080881