Pitfalls of X-chromosome inactivation testing in females with Fabry disease
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11110/22:10443368 RIV/00064190:_____/22:N0000015
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Pitfalls of X-chromosome inactivation testing in females with Fabry disease
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30101 - Human genetics
Result continuities
Project
<a href="/en/project/NU21-08-00324" target="_blank" >NU21-08-00324: Evaluation of new biomarkers of Fabry disease in selected groups of patients in the Czech Republic</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
American Journal of Medical Genetics: Part A
ISSN
1552-4825
e-ISSN
1552-4833
Volume of the periodical
188
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
1979-1989
UT code for WoS article
000773215500001
EID of the result in the Scopus database
2-s2.0-85127276224