ZAP70-Linked severe combined immunodeficiency - ZAP70 gene.


Severe combined immunodeficiency linked to ZAP70 (SCID) is an inherited disorder that damages the immune system. This disease is one of several forms of severe combined immunodeficiency, a group of disorders with multiple genetic causes. Affected children have no immune protection against bacteria, viruses and fungi. They are prone to recurrent and persistent infections that can be serious or life threatening. These infections are usually caused by organisms "opportunists" who usually do not cause disease in people with normal immune systems. Affected individuals often have pneumonia, chronic diarrhea and generalized rashes. In addition, they grow much more slowly than healthy children. Without treatment, affected individuals usually survive only one or two years.The most individuals with severe combined immunodeficiency linked to ZAP70 are diagnosed in the first 6 months of life.

This disease is due to mutations in the ZAP70 gene, located on the long arm of chromosome 2 (2q12). The ZAP70 gene, encodes a protein kinase associated with the zeta chain. This protein is part of a signaling pathway that guides the development and activates T cells of the immune system. T cells identify foreign elements and defend the body against infection. The ZAP70 gene is important for development and function of various cell types T. These include cytotoxic T cells (CD8 + T cells), whose functions include the destruction of virus infected cells. The ZAP70 gene is also involved in the activation of T helper cells (CD4 + T cells), which direct and help the immune system functions, influence the activities of other cells of the immune system.

There are more than 12 ZAP70 gene mutations in people with severe combined immunodeficiency linked to ZAP70 (SCID). Mutations in the ZAP70 gene encoding inhibit kinase associated protein zeta or lead to the synthesis of an unstable and nonfunctional protein chain. A loss of the associated protein kinase functional zeta chain results in the absence of CD8 + T cells and an excess of CD4 + T cells inactive. Resulting deficiency of active T cells causes people with severe combined immunodeficiency linked to ZAP70 more susceptible to infection.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with severe combined immunodeficiency linked to ZAP70, by complete PCR amplification of the exons of the ZAP70 gene, 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).