Compromised PAR1 Activation-A Cause for Bleeding in XMEN?

XMEN (X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and N-linked glycosylation [NLG] defect) is a rare monogenetic disease due to MAGT1 pathogenic variants, which is potentially curable by allogeneic blood or bone marrow transplantation (BMT).[1] Affected patients may experience increased bleeding tendency and fatal hemorrhage after BMT has been described.[2] [3] However, bleeding appears disproportionate to the degree of thrombocytopenia, suggesting a qualitative platelet defect.[2] [4] [5] This is the first case report to describe platelet dysfunction in XMEN (three related males with the same novel hemizygous loss-of-function variant in MAGT1 and one unrelated male with a different hemizygous loss-of-function variant in MAGT1) identifying the same qualitative platelet defect which may explain the increased bleeding tendency in these patients.