We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us

Download Mobile App




Genetic Mutations Identified for Rare VEXAS Syndrome

By LabMedica International staff writers
Posted on 23 Mar 2021
VEXAS syndrome is a serious inflammatory condition which develops in men over 50, causing them to become very sick and fatigued, and can be fatal. More...
It was originally thought to be rare, but a new study has identified genetic mutations which indicate that the disease is actually much more common.

VEXAS syndrome causes unexplained fevers, painful skin rashes and affects the bone marrow resulting in a reduced number of red and white blood cells. The disease affects only men because it is caused by genetic mutations on the X chromosome, and men carry only one X chromosome. The mutations are not present at birth; instead they develop during the patient's lifetime.

A multi-center team led by the University of Leeds (Leeds, UK) examined DNA samples to establish the prevalence of the genetic mutations identified when the disease was first discovered in 2020. They screened a cohort of 18 local patients who matched the symptoms and found mutations in 10 of them. Eight had the known variant previously associated with the disease, but two patients had completely different variants. This identified a new way in which the mutations can cause VEXAS, meaning it is likely to be much more common than was currently thought. VEXAS stands for Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome.

The team identified 10 new patients with somatic mutations in UBA1, but only eight had altered p.Met41. A novel variant, c.167C>T; p.Ser56Phe was identified, which was present in myeloid, and not lymphoid lineages and led to preferential loss of the catalytic activity of cytoplasmic UBA1. An additional novel variant, c.118-1G>C was identified at the splice acceptor site of exon 3 leading to altered splicing in vitro. Bone marrow biopsies from two patients with a Met41 substitution and the novel splice site variant were consistent with previously reported features of VEXAS. The bone marrow of the patient with the p.Ser56Phe variant was less similar, likely driven by a distinct but overlapping disease mechanism.

Sinisa Savic, MRCP, FRCPath, PhD, a Clinical Immunologist and a senior author of the study, said, “I have been looking after a number of patients with what we now know is VEXAS syndrome for several years. Their care has been complicated by the fact that we did not have a diagnosis which made choosing their treatment and advising them about the prognosis very difficult. Having established the cause of VEXAS we now have a real opportunity to transform the care of these patients. We know there are still many patients who have a VEXAS-like condition, but in whom we do not know the cause.”

The authors concluded that their study confirms somatic p.Met41 substitutions in UBA1 as a major cause of VEXAS syndrome and identifies two new disease causing mutations. The study was published on March 9, 2021 in the journal Blood Advances.

Related Links:
University of Leeds


Gold Member
Antipsychotic TDM Assays
Saladax Antipsychotic Assays
Portable Electronic Pipette
Mini 96
Specimen Radiography System
TrueView 200 Pro
New
Alcohol Testing Device
Dräger Alcotest 7000
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








Channels

Hematology

view channel
Image: New research points to protecting blood during radiation therapy (Photo courtesy of 123RF)

Pioneering Model Measures Radiation Exposure in Blood for Precise Cancer Treatments

Scientists have long focused on protecting organs near tumors during radiotherapy, but blood — a vital, circulating tissue — has largely been excluded from dose calculations. Each blood cell passing through... Read more

Immunology

view channel
Image: The VENTANA HER2 (4B5) test is now CE-IVDR approved (Photo courtesy of Roche)

Companion Diagnostic Test Identifies HER2-Ultralow Breast Cancer and Biliary Tract Cancer Patients

Breast cancer is the most common cancer in Europe, with more than 564,000 new cases and 145,000 deaths annually. Metastatic breast cancer is rising in younger populations and remains the leading cause... Read more

Pathology

view channel
Image: An adult fibrosarcoma case report has shown the importance of early diagnosis and targeted therapy (Photo courtesy of Sultana and Sailaja/Oncoscience)

Accurate Pathological Analysis Improves Treatment Outcomes for Adult Fibrosarcoma

Adult fibrosarcoma is a rare and highly aggressive malignancy that develops in connective tissue and often affects the limbs, trunk, or head and neck region. Diagnosis is complex because tumors can mimic... Read more

Technology

view channel
Image: Conceptual design of the CORAL capsule for microbial sampling in the small intestine (H. Mohammed et al., Device (2025). DOI: 10.1016/j.device.2025.100904)

Coral-Inspired Capsule Samples Hidden Bacteria from Small Intestine

The gut microbiome has been linked to conditions ranging from immune disorders to mental health, yet conventional stool tests often fail to capture bacterial populations in the small intestine.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.