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Diagnostic challenges for a novel SH2D1A mutation associated with X‐linked lymphoproliferative disease
- Source :
- Pediatric Blood & Cancer. 67
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- 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.
- Subjects :
- Adult
Male
Epstein-Barr Virus Infections
Herpesvirus 4, Human
Mutation, Missense
medicine.disease_cause
Lymphohistiocytosis, Hemophagocytic
Virus
Flow cytometry
03 medical and health sciences
Fatal Outcome
0302 clinical medicine
Signaling Lymphocytic Activation Molecule Family
Humans
Medicine
Signaling Lymphocytic Activation Molecule Associated Protein
Receptor
Gene
Hemizygote
Hemophagocytic lymphohistiocytosis
Mutation
medicine.diagnostic_test
Gene Expression Regulation, Leukemic
business.industry
X-linked lymphoproliferative disease
Hematology
medicine.disease
Molecular biology
Lymphoproliferative Disorders
Neoplasm Proteins
Amino Acid Substitution
Oncology
030220 oncology & carcinogenesis
Pediatrics, Perinatology and Child Health
Phosphorylation
business
030215 immunology
Subjects
Details
- ISSN :
- 15455017 and 15455009
- Volume :
- 67
- Database :
- OpenAIRE
- Journal :
- Pediatric Blood & Cancer
- Accession number :
- edsair.doi.dedup.....bf5bdca6c9c9663e38ac15060b300aad