Antonio Marzollo, Italy
Azienda Ospedaliera - Università di Padova U.O.C. Oncoematologia PediatricaPresenter of 1 Presentation
NOVEL CLINICAL FEATURES OF MAGT1 DEFICIENCY
Abstract
Background and Aims
X-MEN syndrome is a X-linked PID due to loss-of-function mutations in MAGT1 gene, characterized by variable immunological alterations and high risk of lymphoproliferation. We describe four X-MEN patients from two unrelated families carrying novel pathogenic MAGT1 mutations. Targeted therapy with Mg2+ could represent a curative option, although currently HSCT is indicated in presence of lymphoma.
Methods
Next-generation sequence, Flow-cytometry, Western-Blot.
Results
Pt1 (male, 14yo) suffers from isolated hypertension, severe autoimmune hemolytic anemia, recurrent warts and lymphadenomegaly. His older brother (Pt2, 17 yo) suffers from recurrent otitis media, cutaneous warts, and frequent muco-cutaneous HSV-reactivation. Both patients showed EBV-DNA < 1.000 cp/ml and normal CBC and Ig-levels. Increased double negative T-cells and reduced memory B-cells were detected. Pt3 (male, 5yo) was admitted for lymphadenomegaly, recurrent fever, weight loss and night sweats. He had EBV infection without complete seroconversion, decreased B memory cell and poor response to pneumococcal vaccine, and severe thrombocytopenia. Lymph node biopsy was consistent with Hodgkin Lymphoma. His maternal uncle (Pt4) was treated in childhood for non-Hodgkin lymphoma and developed in adult age a severe persistent thrombocytopenia and a second lymphoma.
NGS revealed, in MAGT1 gene, a splice variant (c.628-2A>G) in Pt1 and Pt2 and a variant resulting in a premature stop codon (c.370C>T) in Pt3 and Pt4. In all patients, MAGT1 expression is impaired and results in down-regulation of NKG2D.
Conclusions
X-MEN phenotype is extremely variable requiring different specialist to reach early diagnosis and institute a personalized therapy; in this context NKG2D evaluation could be represent a useful diagnostic marker.