Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
Pediatr Blood Cancer
; 67(4): e28184, 2020 04.
Article
en 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Herpesvirus Humano 4
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Infecciones por Virus de Epstein-Barr
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Mutación Missense
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Linfohistiocitosis Hemofagocítica
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Hemicigoto
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Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria
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Trastornos Linfoproliferativos
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Proteínas de Neoplasias
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Humans
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Male
Idioma:
En
Año:
2020
Tipo del documento:
Article