Severe combined immunodeficiency, autosomal recessive, negative T cells, B cells negative, positive NK cells (severe combined immunodeficiency, autosomal recesive, negative T-cell, B-cell negative, positive NK cell) - RAG1 and RAG2 Genes.
Severe combined immunodeficiency (SCID) encompasses a genetically and clinically heterogeneous group of disorders with a defective immune cell function and humoral. SCID can be divided into two main classes: those (B + SCID) and those without B lymphocytes B lymphocytes (B- SCID). The presence or absence of NK cells varies within these groups. SCID patients present in childhood recurrent and persistent infections with opportunistic organisms, including Candida albicans, Pneumocystis jiroveci, and Cytomegalovirus, among many others. The common feature of all types of SCID is the absence of T cell immunity mediated cell due to a defect in T - cell development Without treatment, patients generally die in the first year of life.
People affected with SCID T-, B-, NK +, present thymic dysplasia, unusual susceptibility to fungi and viruses as well as pyogenic pathogens, lack of delayed hypersensitivity and failure in the production of antibodies. In addition, affected individuals show a deterioration of growth from 3 months old, persistent diarrhea, candiadiasis, lung infections, fever and opportunistic infections. The most common organisms include Candida albicans, Pseudomonas, gram-negative species, Pneumocystis, Streptococcus and Staphylococcus.
This process is due in half of the cases by mutations in the RAG1 gene, located on the short arm of chromosome 11 (11p13) and RAG2, located on the short arm of chromosome 11 (11p13). These genes encode proteins involved in the activation of the recombination of the variable region V (D) J of immunoglobulins during the development of B and T cells in the RAG complex media RAG1 sequences conserved recombination signal (RSS ) DNA binding activities and catalyzes DNA cleavage by introducing a double - strand break between RSS and the adjacent segment encoding. Meanwhile, the RAG2 protein is not a catalytic component, but it is necessary for all known catalytic activities. The RAG complex also plays a role in pre-allelic exclusion of B cells In addition to its endonuclease activity, RAG1 also acts as a protein E3 ubiquitin ligase mediates the addition of a single ubiquitin molecule to histone H3, which which it is required for the binding step V (D) J recombination.
Mutations in RAG1 and RAG2 genes give rise to a functional inability to form antigen receptors through genetic recombination, leading to a complete loss or a marked reduction in the activity of V (D) J recombination.
This disease is inherited in an autosomal recessive pattern, that is, 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 performed in IVAMI: in IVAMI perform the detection of mutations associated with severe combined immunodeficiency, autosomal recessive, negative T cells, B negative cells positive NK cells through the complete PCR amplification of the exons of the RAG1 and RAG2 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).