Pitfalls of X-chromosome inactivation testing in females with Fabry disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F22%3A10443368" target="_blank" >RIV/00064165:_____/22:10443368 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/22:10443368 RIV/00064190:_____/22:N0000015

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.nI6vI_1MG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.nI6vI_1MG</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ajmg.a.62728" target="_blank" >10.1002/ajmg.a.62728</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pitfalls of X-chromosome inactivation testing in females with Fabry disease

Popis výsledku v původním jazyce

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding alpha-galactosidase A (AGAL). The impact of X-chromosome inactivation (XCI) on the phenotype of female FD patients remains unclear. In this study we aimed to determine pitfalls of XCI testing in a cohort of 35 female FD patients. XCI was assessed by two methylation-based and two allele-specific expression assays. The results correlated, although some variance among the four assays was observed. GLA transcript analyses identified crossing-over in three patients and detected mRNA instability in three out of four analyzed null alleles. AGAL activity correlated with XCI pattern and was not influenced by the mutation type or by reduced mRNA stability. Therefore, AGAL activity may help to detect crossing-over in patients with unstable GLA alleles. Tissue-specific XCI patterns in six patients, and age-related changes in two patients were observed. To avoid misinterpretation of XCI results in female FD patients we show that (i) a combination of several XCI assays generates more reliable results and minimizes possible biases; (ii) correlating XCI to GLA expression and AGAL activity facilitates identification of cross-over events; (iii) age- and tissue-related XCI specificities of XCI patterning should be considered.

Název v anglickém jazyce

Pitfalls of X-chromosome inactivation testing in females with Fabry disease

Popis výsledku anglicky

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene encoding alpha-galactosidase A (AGAL). The impact of X-chromosome inactivation (XCI) on the phenotype of female FD patients remains unclear. In this study we aimed to determine pitfalls of XCI testing in a cohort of 35 female FD patients. XCI was assessed by two methylation-based and two allele-specific expression assays. The results correlated, although some variance among the four assays was observed. GLA transcript analyses identified crossing-over in three patients and detected mRNA instability in three out of four analyzed null alleles. AGAL activity correlated with XCI pattern and was not influenced by the mutation type or by reduced mRNA stability. Therefore, AGAL activity may help to detect crossing-over in patients with unstable GLA alleles. Tissue-specific XCI patterns in six patients, and age-related changes in two patients were observed. To avoid misinterpretation of XCI results in female FD patients we show that (i) a combination of several XCI assays generates more reliable results and minimizes possible biases; (ii) correlating XCI to GLA expression and AGAL activity facilitates identification of cross-over events; (iii) age- and tissue-related XCI specificities of XCI patterning should be considered.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

<a href="/cs/project/NU21-08-00324" target="_blank" >NU21-08-00324: Evaluace nových biomarkerů Fabryho choroby u vybraných skupin pacientů v České republice</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

American Journal of Medical Genetics: Part A

ISSN

1552-4825

e-ISSN

1552-4833

Svazek periodika

188

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

1979-1989

Kód UT WoS článku

000773215500001

EID výsledku v databázi Scopus

2-s2.0-85127276224