Novel Somatic UBA1 Variant in a Patient With VEXAS Syndrome

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/23:10466027 RIV/00023736:_____/23:00013511 RIV/00064165:_____/23:10466027

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Somatic UBA1 Variant in a Patient With VEXAS Syndrome

Popis výsledku v původním jazyce

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

Název v anglickém jazyce

Novel Somatic UBA1 Variant in a Patient With VEXAS Syndrome

Popis výsledku anglicky

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

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30226 - Rheumatology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Arthritis Rheumatology.

ISSN

2326-5191

e-ISSN

2326-5205

Svazek periodika

75

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

6

Strana od-do

1285-1290

Kód UT WoS článku

000998914900001

EID výsledku v databázi Scopus

2-s2.0-85159146907