Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
Pediatr Blood Cancer
; 67(4): e28184, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31994322
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Herpesvirus Humano 4
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Infecções por Vírus Epstein-Barr
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Mutação de Sentido Incorreto
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Linfo-Histiocitose Hemofagocítica
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Hemizigoto
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Proteína Associada à Molécula de Sinalização da Ativação Linfocitária
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Transtornos Linfoproliferativos
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Proteínas de Neoplasias
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article