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Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease
Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21‐year‐old patient with fatal...
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| Published in: | Pediatric blood & cancer 2020-04, Vol.67 (4), p.e28184-n/a |
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| container_start_page | e28184 |
| container_title | Pediatric blood & cancer |
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| creator | Torralba‐Raga, Lamberto Tesi, Bianca Chiang, Samuel C. C. Schlums, Heinrich Nordenskjöld, Magnus Horne, AnnaCarin Henter, Jan‐Inge Meeths, Marie Abdelhaleem, Mohamed Weitzman, Sheila Bryceson, Yenan |
| description | Mutations in SH2D1A, encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are associated with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous SH2D1A c.49G > A (p.E17K) variant in a 21‐year‐old patient with fatal Epstein‐Barr virus infection–associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of the SAP variant protein, yet binding to phosphorylated CD244 receptor was reduced by >95%. Three healthy brothers carried the SH2D1A c.49G > A 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 SH2D1A variants and caution in using functional flow cytometry assays for the diagnosis of XLP1. |
| doi_str_mv | 10.1002/pbc.28184 |
| format | article |
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Three healthy brothers carried the SH2D1A c.49G > A variant. Thus, data suggest that this variant represents a pathogenic mutation, but with variable expressivity. 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| subjects | Cell activation diagnostic assays Epstein-Barr virus Flow cytometry Hematology hemophagocytic lymphohistiocytosis Histiocytosis Immunoproliferative diseases Intracellular signalling ITSM Lymphocytes Lymphocytosis Mutation NK cells Oncology Pediatrics SAP SH2D1A protein X‐linked lymphoproliferative disease |
| title | Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease |
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