Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease

被引：7

作者：

Torralba-Raga, Lamberto ^{[1
]}

Tesi, Bianca ^{[2
,3
]}

Chiang, Samuel C. C. ^{[1
]}

Schlums, Heinrich ^{[1
]}

Nordenskjoeld, Magnus ^{[3
]}

Horne, AnnaCarin ^{[4
,5
]}

Henter, Jan-Inge ^{[2
]}

Meeths, Marie ^{[2
,3
]}

Abdelhaleem, Mohamed ^{[6
]}

Weitzman, Sheila ^{[7
,8
]}

Bryceson, Yenan ^{[1
,9
]}

机构：

[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Med,Ctr Hematol & Regenerat Med, S-14186 Stockholm, Sweden

[2] Karolinska Univ, Hosp Solna, Clin Genet, Stockholm, Sweden

[3] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[4] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden

[5] Karolinska Univ Hosp, Paediat Rheumatol Dept, Stockholm, Sweden

[6] Hosp Sick Children, Dept Paediat, Lab Med, Toronto, ON, Canada

[7] Hosp Sick Children, Div Pediat Hematol Oncol, Toronto, ON, Canada

[8] Univ Toronto, Toronto, ON, Canada

[9] Univ Bergen, Inst Clin Sci, Broegelmann Res Lab, Bergen, Norway

来源：

PEDIATRIC BLOOD & CANCER | 2020年 / 67卷 / 04期

基金：

欧洲研究理事会; 瑞典研究理事会;

关键词：

diagnostic assays; hemophagocytic lymphohistiocytosis; ITSM; NK cells; SAP; X-linked lymphoproliferative disease; INFECTION; GENE; SAP; CYTOTOXICITY; ACTIVATION; RECEPTORS; DOMAIN;

D O I：

10.1002/pbc.28184

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：5

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