X-linked lymphoproliferative disease
| X-linked lymphoproliferative disease | |
|---|---|
| Classification and external resources | |
| Specialty | Lua error in Module:Wikidata at line 446: attempt to index field 'wikibase' (a nil value). |
| ICD-10 | D82.3 |
| OMIM | 308240 300635 |
| DiseasesDB | 3998 |
| eMedicine | med/1370 |
| Patient UK | X-linked lymphoproliferative disease |
| MeSH | D008232 |
| 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
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ http://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ X-linked Lymphoproliferative Syndrome at Merck Manual of Diagnosis and Therapy Professional Edition
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lymphoproliferative Disorders at eMedicine
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
