X - linked lymphoproliferative, disease ... disease (Duncan) (X - linked lymphoproliferative disease) - Genes SH2D1A and XIAP.
The X - linked lymphoproliferative disease (XLP) chromosome is an alteration of the immune system and blood cells that affects almost exclusively boys. More than half of individuals with this condition produce an immune response to the Epstein-Barr virus (EBV). In some people, the EBV causes infectious mononucleosis. Normally after initial infection, EBV remains latent in B cells, controlled by that specifically target B cells infected with EBV T cells.
Individuals with X - linked lymphoproliferative disease may respond to EBV infection by encoding high amounts of T cells, B cells, and macrophages. This proliferation of immune cells often causes a reaction called hemophagocytic lymphohistiocytosis threatening, causing fever, destroy hematopoietic cells in bone marrow, and liver damage. Spleen, heart, kidneys and other organs and tissues may also be affected. In some individuals with XLP, hemophagocytic lymphohistiocytosis or other related EBV infection without symptoms may develop. About a third of people with X - linked lymphoproliferative, they have dysgammaglobulinemia, ie they have abnormal concentrations of certain types of immunoglobulins. Dysgammaglobulinemia individuals are prone to recurrent infections. In addition, one - third of individuals with XLP lymphomas develop. Without treatment, most people with XLP survive only in childhood. Death is usually caused by hemophagocytic lymphohistiocytosis.
XLP1 (also known as classic XLP) and XLP2: based on their genetic cause and pattern of signs and symptoms, two types of X - linked lymphoproliferative distinguished. In general, people with XLP2 are more likely to develop hemophagocytic lymphohistiocytosis without EBV infection, splenomegaly and colitis. Individuals with this type of disease do not develop lymphoma.
This disease is due to mutations in the SH2D1A and XIAP genes. Mutations in the gene give rise to SH2D1A XLP1 type of disease. Mutations in the gene give rise to XIAP XLP2 type of disease.
The SH2D1A gene, located on the long arm of the X (Xq25) chromosome, encodes the SAP protein, involved in the operation of cytotoxic lymphocytes and is necessary for the development of T cell SAP protein, also it helps control reactions immune triggering apoptosis of cytotoxic lymphocytes when they are no longer needed. They have identified more than 70 mutations in the SH2D1A gene in individuals with X - linked lymphoproliferative disease (XLP). Mutations in the gene impair the function of the SAP protein, result in an abnormally short protein is unstable or nonfunctional, or prevent any protein coding. The loss of functional protein alters the proper signaling in the immune system and can prevent the control body in the immune responses against EBV infection and lead to the development of lymphomas.
The XIAP gene, located on the long arm of the X (Xq25) chromosome, encodes a protein that helps protect cells from apoptosis in response to certain signals inhibiting the action of caspase enzymes, necessary for apoptosis. Specifically, the XIAP protein inhibits caspase enzymes 3, 7 and 9. This protein also plays a role in other signaling pathways that are involved in various functions in the body. Mutations in the gene give rise to an absence of XIAP protein or decrease the amount of protein that is encoded. It is unclear how the lack of this protein leads to the signs and symptoms of the disease.
This disease usually inherited recessive pattern with an X - linked In males, an altered copy of a gene associated in each cell is sufficient to cause disease. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In women, a mutation must occur in both copies of the gene to cause the disorder. Because it is unlikely that women have two altered copies of a gene associated, males are affected by X - linked recessive disorders much more frequently than women. However, in rare cases, a woman who has an altered copy of SH2D1A XIAP gene or gene in each cell can develop signs and symptoms of this disease.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with X - linked lymphoproliferative by the complete PCR amplification of the exons of SH2D1A and XIAP genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).