Abstract
XMEN (X-linked immunodeficiency with magnesium defect) is caused by loss-of-function mutations in MAGT1 which is encoded on the X chromosome. The disorder is characterised by CD4 lymphopenia, severe chronic viral infections and defective T-lymphocyte activation. XMEN patients are susceptible to Epstein-Barr virus infections and persistently low levels of intracellular Mg2+. Here we describe a patient that presented with multiple recurrent infections and a subsequent diffuse B-cell lymphoma. Molecular genetic analysis by exome sequencing identified a novel hemizygous MAGT1 nonsense mutation c.1005T>A (NM_032121.5) p.(Cys335*), confirming a diagnosis of XMEN deficiency. Follow-up immunophenotyping was performed by antibody staining and flow cytometry; proliferation was determined by 3H-thymidine uptake after activation by PHA and anti-CD3. Cytotoxic natural killer cell activity was assessed with K562 target cells using the NKTESTTM assay. While lymphocyte populations were superficially intact, B cells were largely naive with a reduced memory cell compartment. Translated NKG2D was absent on both NK and T cells in the proband, and normally expressed in the carrier mother. In vitro NK cell activity was intact in both the proband and his mother. This report adds to the growing number of identified XMEN cases, raising awareness of a, still rare, X-linked immunodeficiency.
Highlights
X-linked immunodeficiency with magnesium defect (XMEN; OMIM: 300853) is a complex primary immunodeficiency (PID) caused by pathogenic loss-of-function variants in Magnesium transporter 1 (MAGT1) [1]
It was noted that from a young age he had ongoing issues with widespread disseminated scarring molluscum contagiosum, with more than 100 lesions at its peak. His mother reported that he had previously suffered from a prolonged outbreak of varicella-zoster virus, with new lesions forming over a 2-week period
In an effort to curtail the “diagnostic odyssey” faced by many rare disease patients, mainstream clinical modalities have embraced the widespread availability of molecular genetic testing
Summary
X-linked immunodeficiency with magnesium defect (XMEN; OMIM: 300853) is a complex primary immunodeficiency (PID) caused by pathogenic loss-of-function variants in MAGT1 [1]. T-cell function defects have been observed; these include absence of the natural killer stimulatory receptor, NKG2D, on both natural killer (NK) and CD8+ T cells [2]. Either MAGT1 or its homologue TUSC3, associate with the enzymatic subunit of the OST complex, STT3B, prior to the post-transitional transfer of glycans to the N-linked glycosylation site. Mutations in MAGT1 manifest as an immunological disorder, despite the functional effect being primarily associated with defective glycosylation. This was recently demonstrated in a cohort of 23 XMEN-confirmed patients [5]. This receptor plays a crucial role in NK cell activation following EBV infection [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
