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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10499272 RIV/00216208:11120/25:43928600 RIV/00216208:11130/25:10499272 RIV/00216208:11150/25:10499272 a 5 dalších

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30217 - Urology and nephrology

Projekt

<a href="/cs/project/EF16_026%2F0008448" target="_blank" >EF16_026/0008448: Analýza českých genomů pro teranostiku</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Clinical Kidney Journal

ISSN

2048-8505

e-ISSN

2048-8513

Svazek periodika

18

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

sfaf167

Kód UT WoS článku

001518589600001

EID výsledku v databázi Scopus

2-s2.0-105009080881