PMID- 31994322
OWN - NLM
STAT- MEDLINE
DCOM- 20200629
LR  - 20200629
IS  - 1545-5017 (Electronic)
IS  - 1545-5009 (Linking)
VI  - 67
IP  - 4
DP  - 2020 Apr
TI  - Diagnostic challenges for a novel SH2D1A mutation associated with X-linked 
      lymphoproliferative disease.
PG  - e28184
LID - 10.1002/pbc.28184 [doi]
AB  - 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.
CI  - (c) 2020 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.
FAU - Torralba-Raga, Lamberto
AU  - Torralba-Raga L
AD  - Department of Medicine, Centre for Hematology and Regenerative Medicine, 
      Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 
      Sweden.
FAU - Tesi, Bianca
AU  - Tesi B
AD  - Clinical Genetics, Karolinska University Hospital Solna, Stockholm, Sweden.
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Chiang, Samuel C C
AU  - Chiang SCC
AD  - Department of Medicine, Centre for Hematology and Regenerative Medicine, 
      Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 
      Sweden.
FAU - Schlums, Heinrich
AU  - Schlums H
AD  - Department of Medicine, Centre for Hematology and Regenerative Medicine, 
      Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 
      Sweden.
FAU - Nordenskjold, Magnus
AU  - Nordenskjold M
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Horne, AnnaCarin
AU  - Horne A
AD  - Department of Women's and Children's Health, Karolinska University Hospital, 
      Stockholm, Sweden.
AD  - Paediatric Rheumatology Department, Karolinska University Hospital, Stockholm, 
      Sweden.
FAU - Henter, Jan-Inge
AU  - Henter JI
AD  - Clinical Genetics, Karolinska University Hospital Solna, Stockholm, Sweden.
FAU - Meeths, Marie
AU  - Meeths M
AD  - Clinical Genetics, Karolinska University Hospital Solna, Stockholm, Sweden.
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Abdelhaleem, Mohamed
AU  - Abdelhaleem M
AD  - Department of Paediatric Laboratory Medicine, Hospital for Sick Children, 
      Toronto, Canada.
FAU - Weitzman, Sheila
AU  - Weitzman S
AD  - Division of Pediatric Hematology/Oncology, The Hospital for Sick Children and the 
      University of Toronto, Toronto, Canada.
FAU - Bryceson, Yenan
AU  - Bryceson Y
AUID- ORCID: 0000-0002-7783-9934
AD  - Department of Medicine, Centre for Hematology and Regenerative Medicine, 
      Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, 
      Sweden.
AD  - Broegelmann Research Laboratory, Institute of Clinical Sciences, University of 
      Bergen, Bergen, Norway.
LA  - eng
GR  - 311335/ERC_/European Research Council/International
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200129
PL  - United States
TA  - Pediatr Blood Cancer
JT  - Pediatric blood & cancer
JID - 101186624
RN  - 0 (CD244 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (SH2D1A protein, human)
RN  - 0 (Signaling Lymphocytic Activation Molecule Associated Protein)
RN  - 0 (Signaling Lymphocytic Activation Molecule Family)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution
MH  - *Epstein-Barr Virus Infections/genetics/metabolism
MH  - Fatal Outcome
MH  - Gene Expression Regulation, Leukemic
MH  - *Hemizygote
MH  - *Herpesvirus 4, Human/genetics/metabolism
MH  - Humans
MH  - *Lymphohistiocytosis, Hemophagocytic/genetics/metabolism/virology
MH  - *Lymphoproliferative Disorders/genetics/metabolism/virology
MH  - Male
MH  - *Mutation, Missense
MH  - *Neoplasm Proteins/genetics/metabolism
MH  - *Signaling Lymphocytic Activation Molecule Associated 
      Protein/biosynthesis/genetics
MH  - Signaling Lymphocytic Activation Molecule Family/genetics
OTO - NOTNLM
OT  - ITSM
OT  - NK cells
OT  - SAP
OT  - X-linked lymphoproliferative disease
OT  - diagnostic assays
OT  - hemophagocytic lymphohistiocytosis
EDAT- 2020/01/30 06:00
MHDA- 2020/07/01 06:00
CRDT- 2020/01/30 06:00
PHST- 2019/06/13 00:00 [received]
PHST- 2019/12/19 00:00 [revised]
PHST- 2019/12/27 00:00 [accepted]
PHST- 2020/01/30 06:00 [pubmed]
PHST- 2020/07/01 06:00 [medline]
PHST- 2020/01/30 06:00 [entrez]
AID - 10.1002/pbc.28184 [doi]
PST - ppublish
SO  - Pediatr Blood Cancer. 2020 Apr;67(4):e28184. doi: 10.1002/pbc.28184. Epub 2020 
      Jan 29.