Absence of SLAM mutations in EBV‐associated lymphoproliferative disease patients

  title={Absence of SLAM mutations in EBV‐associated lymphoproliferative disease patients},
  author={V{\'e}ronique Ferrand and Cui-Lin Li and Giovanni Romeo and Luo Yin},
  journal={Journal of Medical Virology},
X‐linked lymphoproliferative disease is a rare inherited immunodeficiency in which affected males present abnormal responses to Epstein‐Barr virus (EBV) infection. The gene defective in X‐linked lymphoproliferative disease, SH2D1A (also named SAP or DSHP), has been identified and shown to code for an adapter protein that interacts with signaling lymphocytic activation molecule (SLAM) and several other members of the CD2 superfamily. SH2D1A is mutated in no more than 60% of X‐linked… 

The Association of CD46, SLAM and CD209 Cellular Receptor Gene SNPs with Variations in Measles Vaccine-Induced Immune Responses: A Replication Study and Examination of Novel Polymorphisms

Understanding the functional and mechanistic consequences of these genetic polymorphisms on immune response variations could assist in directing new measles and potentially other viral vaccine design, and in better understanding measles immunogenetics.

Molecular and cellular pathogenesis of X‐linked lymphoproliferative disease

In XLP patients who lack functional SAP, the SLAM family receptors may not signal properly, which likely contributes to the phenotypes of XLP, including fulminant infectious mononucleosis, lymphoma, and hypogammaglobulinemia.



Diagnosis of X‐linked lymphoproliferative disease by analysis of SLAM‐associated protein expression

X‐linked lymphoproliferative disease should be suspected in certain boys previously diagnosed as having CVID and patients are recommended to be investigated both by genetic analysis of SH2D1A and by expression of SAP protein.

Structural basis for SH2D1A mutations in X-linked lymphoproliferative disease.

A single-strand conformation polymorphism assay for mutation analysis in XLP is described and four novel patients with SH2D1A mutations are described.

Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome.

  • K. NicholsD. Harkin D. Haber
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
Observations confirm the identity of DSHP as the gene responsible for XLP, and suggest a role in the regulation of lymphocyte activation and proliferation, while its inactivation in XLP patients results in a selective immunodeficiency to EBV.

SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients

The identification of SH2D1A mutations in carriers from all three XLP families screened and the detection of mutations in two out of eight atypical patients indicates the usefulness of a DNA-based diagnosis for XLP disease.

Correlation of mutations of the SH2D1A gene and epstein-barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease.

It was found that mutations in the SH2D1A gene are responsible for XLP but that there is no correlation between genotype and phenotype or outcome and unidentified factors, either environmental or genetic, contribute to the pathogenesis of XLP.

The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B.

It is reported that SH2D1A associates with Dok1, a protein that interacts with Ras-GAP, Csk, and Nck, and can affect multiple intracellular signaling pathways that are potentially important in the normal effective host response to Epstein-Barr virus infection.

Epstein-Barr virus-negative boys with non-Hodgkin lymphoma are mutated in the SH2D1A gene, as are patients with X-linked lymphoproliferative disease (XLP).

Development of dysgamma-globulinaemia and lymphoma without evidence of prior EBV infection in four of the authors' patients suggests that EBV is unrelated to these phenotypes, in contrast to fulminant or fatal infectious mononucleosis.

Recurrent B‐cell non‐Hodgkin's lymphoma in two brothers with X‐linked lymphoproliferative disease without evidence for Epstein–Barr virus infection

It is postulate that the genetic defect and the following dysregulation of the B‐/T‐cell interaction rendered these patients susceptible to the early onset of B‐cell NHL and that EBV infection is not an obligate prerequisite.

X-Linked Lymphoproliferative Disease: Twenty-Five Years after the Discovery

The X-linked lymphoproliferative disease (XLP), one of six described X-linked immunodeficiencies, stems from a mutation at Xq25 which renders males impotent to mount an effective immune response to

Malignant lymphoma in the X‐linked lymphoproliferative syndrome

Characteristics that distinguish ML in XLP from other ML include a maternal family history of XLP, early age of onset, acquired hypogammaglobulinemia, post‐EBV infection, and ileocecal involvement.