Test Code UBA1Q UBA1 Mutation Quantitative Detection, VEXAS syndrome, Droplet Digital PCR, Varies
Ordering Guidance
This test is intended for patients with clinical symptoms and other pertinent laboratory findings raising concern for VEXAS syndrome. These may include, but are not limited to, systemic or localized (eg, ear, orbital, skin) tissue inflammation presenting as rheumatologic disease, abnormal (usually low) whole blood counts, macrocytic anemia, characteristic microscopic changes in the bone marrow, as well as others.
Shipping Instructions
1. Both refrigerated and ambient specimens must arrive within 7 days of collection.
2. Collect and package specimen as close to shipping time as possible.
Necessary Information
The following information is required:
1. Pertinent clinical history
2. Date of collection
3. Specimen source (blood or bone marrow)
Specimen Required
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD-B) or green top (heparin)
Specimen Volume: 4 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
3. Label specimen as blood.
Specimen Stability: Refrigerated 7 days/Ambient 7 days
Specimen Type: Bone marrow aspirate
Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Yellow top (ACD-B) or green top (heparin)
Specimen Volume: 2 mL
Collection Instructions:
1. Invert several times to mix bone marrow.
2. Send bone marrow specimen in original tube. Do not aliquot.
3. Label specimen as bone marrow.
Specimen Stability: Refrigerated 7 days/Ambient 7 days
Specimen Type: Extracted DNA from blood or bone marrow
Container/Tube: 1.5- to 2-mL tube with indication of volume and concentration of DNA
Specimen Volume: Entire specimen
Collection Instructions:
1. Label specimen as extracted DNA and source of specimen
2. Indicate volume and concentration of DNA on label. The required volume of DNA is at least 50 mcL at a concentration of 50 ng/mcL
Specimen Stability: Frozen (preferred)/Refrigerated
Forms
1. Hematopathology Patient Information (T676)
2. If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
Useful For
Identification of pathogenic variant(s) in the UBA1 gene in patients presenting with symptoms concerning for or consistent with VEXAS syndrome
Special Instructions
Method Name
Droplet Digital Polymerase Chain Reaction
Reporting Name
UBA1 Mutation, Quant, ddPCR, VSpecimen Type
VariesSpecimen Minimum Volume
Whole blood: 4 mL
Bone marrow: 2 mL
Extracted DNA: 50 mcL at 50 ng/mcL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Refrigerated (preferred) | 7 days | |
Ambient | 7 days |
Reject Due To
Gross hemolysis | Reject |
Moderately to severely clotted | Reject |
Clinical Information
VEXAS syndrome is caused by somatic mutations in the UBA1 gene, which is located on the X-chromosome and encodes ubiquitin-activating enzyme E1, an important component in the protein ubiquitylation process. This syndrome, identified in 2020, is characterized by adult-onset rheumatologic and hematologic manifestations. Inflammatory disease can present systemically, as well with more localized findings involving the orbit, skin or ears. Hematologic abnormalities are frequently present, including low blood counts, macrocytic anemia, and characteristic vacuolated myeloid and erythroid precursor cells in the bone marrow.(1) VEXAS syndrome occurs overwhelmingly in male patients, suggesting that biologic females who might acquire a UBA1 mutation may be relatively protected by the presence of the remaining normal wild type allele.(2) To date, nearly all documented cases of VEXAS syndrome have been caused by seven mutations that occur at three different sites within exon 3 of the UBA1 gene: the intron 2 acceptor splice site and p.Met41 codon region (c.118-122), and the p.Ser56 codon (c.167).(1-4) Importantly, a significant number of VEXAS patients may have predisposition to develop bone marrow failure, clonal hematopoiesis, myelodysplastic syndrome, or other hematologic neoplasms (eg, plasma cell neoplasms).(2-4) Patients with UBA1 mutation and features of bone marrow failure appear to be associated with poor prognosis and may not respond to standard immunosuppressive and hypomethylating agents typically utilized in the treatment of autoinflammatory disorders and myelodysplastic syndrome.(3,4) Testing for these mutations will serve to identify VEXAS syndrome patients who should be considered for alternative therapies or clinical trials.
Reference Values
An interpretive report will be provided.
Day(s) Performed
Monday through Saturday
Report Available
4 to 8 daysPerforming Laboratory
Mayo Clinic Laboratories in RochesterTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
81479