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X-linked lymphoproliferative disease

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Title: X-linked lymphoproliferative disease  
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Subject: List of eponymously named diseases, ICD-10 Chapter III: Diseases of the blood and blood-forming organs, and certain disorders involving the immune mechanism, Hemophagocytic lymphohistiocytosis, XIAP
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X-linked lymphoproliferative disease

X-linked lymphoproliferative disease
Classification and external resources
ICD-10 OMIM DiseasesDB eMedicine MeSH GeneReviews

X-linked lymphoproliferative disease (also known as "Duncan's disease"[1]:86 or "Purtilo syndrome"[2]) is a lymphoproliferative disorder.[3]

Causes

XLP1

There is a mutation on the X-chromosome that has been found to be associated with a T- and NK-cell lymphoproliferative disorder. The mutation is on the long arm of the chromosome, at position 25, which is denoted as Xq25. At this position, there is a deletion in the SH2D1A gene, which codes for an SH2 domain on a signal transducing protein called SLAM-associated protein (SAP).

The term "SH2" domain stands for src-homology 2 domain, which is a three-dimensional domain structure of about 100 amino acid residues. These domains are present in many signalling proteins because they permit specific, non-covalent bonding to proteins that contain phosphotyrosines. The amino acid residues adjacent to the phosphotyrosine on the target protein are what determine the unique binding specificity.[4]

The SAP protein is important in the signalling events that activate T- and NK-cells[5] due to its adaptor function. Normally, the SAP protein is expressed in the cytoplasm of T- and NK-cells, where it binds to the cytoplasmic domain of the surface receptor called signaling lymphocyte activation molecule (SLAM). This binding initiates a signal transduction pathway, which results in the modulation of IFN-γ. A deletion in the SH2D1A gene leads to a non-functional SH2 domain on the SAP protein, making it unable to bind to SLAM. This leads to aberrant IFN-γ modulation, causing uncontrolled cell proliferation.

XLP2

A second form is associated with XIAP.[6]

Some sources recommend classifying this condition as "X-linked familial hemophagocytic lymphohistiocytosis" instead of X-linked lymphoproliferative disease.[7]

Presentation

Strangely, in boys with X-linked lymphoproliferative disorder, there is an inability to mount an immune response to the Epstein-Barr virus (EBV),[8] which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.[9]

Patients produce insufficient numbers of CD27 memory B cells.[10]

References

External links

  • X-linked lymphoproliferative disease community
  • XLP Research Trust
  • GeneReview/NIH/UW entry on Lymphoproliferative Disease, X-Linked

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