Novel Somatic UBA1 Variant in a Patient With VEXAS Syndrome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F23%3AN0000054" target="_blank" >RIV/00023728:_____/23:N0000054 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10466027 RIV/00023736:_____/23:00013511 RIV/00064165:_____/23:10466027
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/art.42471" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/art.42471</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/art.42471" target="_blank" >10.1002/art.42471</a>
Alternative languages
Result language
angličtina
Original language name
Novel Somatic UBA1 Variant in a Patient With VEXAS Syndrome
Original language description
Somatic mutations in UBA1 have recently been causally linked to a severe adult-onset inflammatory condition referred to as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Ubiquitin-activating enzyme E1 (UBA-1) is of fundamental importance to the modulation of ubiquitin homeostasis and to the majority of downstream ubiquitylation-dependent cellular processes. Direct sequencing analysis of exon 3 containing the prevalent variants p.Met41Leu, p.Met41Val, and/or p.Met41Thr is usually used to confirm the disease-associated mutations. We studied the clinical, biochemical, and molecular genetic characteristics of a 59-year-old man with a 2-year history of arthritis, fever, night sweats, nonspecific skin rash, lymphadenopathy, and myelodysplastic syndrome with multilineage dysplasia. The mutational analysis revealed a previously undescribed sequence variant c.1430G>C in exon 14 (p.Gly477Ala) in the gene UBA1. In vitro enzymatic analyses showed that p.Gly477Ala led to both decreased E1 ubiquitin thioester formation and E2 enzyme charging. We report a case of a patient of European ancestry with clinical manifestations of VEXAS syndrome associated with a newly identified dysfunctional UBA-1 enzyme variant. Due to the patient's insufficient response to various immunosuppressive treatments, allogeneic hematopoietic stem cell transplantation was performed, which resulted in significant improvement of clinical and laboratory manifestations of the disease
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
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OECD FORD branch
30226 - Rheumatology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Arthritis Rheumatology.
ISSN
2326-5191
e-ISSN
2326-5205
Volume of the periodical
75
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
6
Pages from-to
1285-1290
UT code for WoS article
000998914900001
EID of the result in the Scopus database
2-s2.0-85159146907