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
Collection and Transport System
PurSafe Plus®
Automated Chemiluminescence Immunoassay Analyzer
MS-i3080
Laboratory Software
ArtelWare
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 evidence shows viscoelastic testing can improve assessment of blood clotting during postpartum hemorrhage (Photo courtesy of 123RF)

Viscoelastic Testing Could Improve Treatment of Maternal Hemorrhage

Postpartum hemorrhage, severe bleeding after childbirth, remains one of the leading causes of maternal mortality worldwide, yet many of these deaths are preventable. Standard care can be hindered by delays... Read more

Immunology

view channel
Image: The CloneSeq-SV approach can allow researchers to study how cells within high-grade serous ovarian cancer change over time (Photo courtesy of MSK)

Blood Test Tracks Treatment Resistance in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is often diagnosed at an advanced stage because it spreads microscopically throughout the abdomen, and although initial surgery and chemotherapy can work, most... Read more

Industry

view channel
Image: The collaboration aims to improve access to Hb variant testing with the Gazelle POC diagnostic platform (Photo courtesy of Hemex Health)

Terumo BCT and Hemex Health Collaborate to Improve Access to Testing for Hemoglobin Disorders

Millions of people worldwide living with sickle cell disease and other hemoglobin disorders experience delayed diagnosis and limited access to effective care, particularly in regions where testing is scarce.... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.