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We identified a novel hemizygous <jats:italic>SH2D1A<\/jats:italic> c.49G\u00a0&gt;\u00a0A (p.E17K) variant in a 21\u2010year\u2010old patient with fatal Epstein\u2010Barr virus infection\u2013associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by &gt;95%. Three healthy brothers carried the <jats:italic>SH2D1A<\/jats:italic> c.49G\u00a0&gt;\u00a0A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. Importantly, our results highlight challenges in the clinical interpretation of <jats:italic>SH2D1A<\/jats:italic> variants and caution in using functional flow cytometry assays for the diagnosis of XLP1.<\/jats:p>","DOI":"10.1002\/pbc.28184","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T08:59:18Z","timestamp":1580288358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Diagnostic challenges for a novel <i>SH2D1A<\/i> mutation associated with X\u2010linked lymphoproliferative disease"],"prefix":"10.1002","volume":"67","author":[{"given":"Lamberto","family":"Torralba\u2010Raga","sequence":"first","affiliation":[{"name":"Department of Medicine, Centre for Hematology and Regenerative Medicine, Karolinska Institutet Karolinska University Hospital Huddinge  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Karolinska University Hospital Solna  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel C. 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