Atypical splice-site mutations causing VEXAS syndrome

Templé, Marie; Duroyon, Eugénie; Croizier, Carolyne; Rossignol, Julien; Huet, Thomas; Friedrich, Chloé; Zalmai, Loria; Priollet, P.; Hayem, Gilles; Tournillhac, Olivier; Guenno, G. Le; Hermine, Olivier; Terrier, B.; Kosmider, Olivier

doi:10.1093/rheumatology/keab524

Cited by 48 publications

(34 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All patients underwent a biological collection including a genomic DNA extraction from leukocyte pellet. In the present study, exon 3 of UBA1 , as in previous studies 1,7,8 was sequenced in all men older than 50 years old included in the Georges Pompidou European Hospital Centre, Paris, France. Continuous data are expressed as median and interquartile range (IQR; 25th–75th percentiles).…”

Section: N = 97mentioning

confidence: 95%

Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study

Khider

Templé

Bally

et al. 2022

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

Section: N = 97mentioning

confidence: 95%

Systematic search for the UBA1 mutation in men after a first episode of venous thromboembolism: A monocentric study

Khider

Templé

Bally

et al. 2022

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

“…The number of vacuoles is heterogeneous between patients. The a uole should not be a criterion for exclusion of VEXAS diagnosis since som not show vacuole on a bone marrow smear [9,14]. From a functional point of view, the UBA1 gene codes for the enzym zyme E1, are involved in the initiation of the protein ubiquitylation proc translational modification is essential in the regulation of protein turno those involved in the cell cycle, cell death, signal transduction, etc., by all be sent to the proteasome, a protein degradation organelle.…”

Section: Vexas Syndromementioning

confidence: 99%

“…The 3 most frequent mutations affect methionine 41 of exon 3 of UBA1: p.M41T (c.122T>C), p.M41V (c.121A>G) and p.M41L (c.121A>C). Since then other mutations have been reported, such as Splice region mutations at exon 3 (c.118-2A>C and c.118-1G>C) [ 8 ] and (c.118- 9_118-2del) [ 9 ] as well as a mutation affecting codon 56 (c.167C>T) in a patient with a less marked clinical syndrome, have also been reported [ 10 ]. All these mutations are shown in Figure 1 .…”

Section: Vexas Syndromementioning

confidence: 99%

See 1 more Smart Citation

VEXAS Syndrome: A Novelty in MDS Landscape

Templé

Kosmider

2022

Diagnostics

Self Cite

View full text Add to dashboard Cite

Fever, inflammation and vacuoles in hematopoietic cells represent the main features associated with VEXAS syndrome, a new prototype of autoinflammatory disorders genetically characterized by somatic mutation of the UBA1 gene which encodes the enzyme1-activating enzyme (E1) required for ubiquitin signaling. Described very recently, patients with VEXAS syndrome present a systemic autoinflammatory syndrome associated with hematological impairments, especially cytopenias whose pathophysiology is mainly non-elucidated. Initially diagnosed in elderly male patients, VEXAS syndrome was frequently associated with a diagnosis of myelodysplastic syndromes (MDS) leading the medical community to first consider VEXAS syndrome as a new subtype of MDS. However, since the first description of VEXAS patients in 2021, it appears from the multitude of case reports that MDS associated with VEXAS are different from the classically described MDS.

show abstract

“…The next most common location for VEXAS mutations is the canonical splice acceptor site of UBA1 exon 3. Mutations affecting either of the immediate 2 base pairs preceding the exon (c.118-1 and c.118-2), or deletion of 8bp in the splice acceptor site (c.118-9_118-2del) account for 6% of known cases (8,16,24). As with the p.Met41 substitution mutations, mutation of the splice acceptor site leads to a reduction of cytoplasmic UBA1.…”

Section: Splice Acceptor Mutationsmentioning

confidence: 99%