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...

Full description

Saved in:
Bibliographic Details
Published in:Pediatric blood & cancer 2020-04, Vol.67 (4), p.e28184-n/a
Main Authors: 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
Format: Article
Language:English
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.28184