Autosomal recessive hyper-IgE syndrome ... (Autosomal recessive hyper-IgE syndrome) - Gen DOCK8.
The hyper-IgE syndrome autosomal recessive (AR-HIES) is a disorder of the immune system. A characteristic feature of this disease is the development of serious recurrent infections that can be potentially fatal.
Skin infections can be caused by bacteria, viruses or fungi. These infections cause rashes, blisters, abscesses and open wounds. People with AR-HIES also tend to have frequent episodes of pneumonia and other infections of the airways. Other problems with the immune system in persons with AR-HIES include eczema, food or environmental allergies, and asthma. In some affected individuals, the malfunctioning immune system causes an autoimmune disease. For example, autoimmunity may result in hemolytic anemia in persons with AR-HIES.
The hyper-IgE syndrome autosomal recessive (AR-HIES) is characterized by abnormally high levels of immunoglobulin E (IgE) in the blood. The levels of this protein are more than 10 times higher than normal concentrations. IgE normally triggers an immune response against foreign invaders in the body, especially helminths, and also plays a role in allergies. However, it is not clear why people with RA-HIES have such high concentrations of this protein. In addition, those affected have eosinophilia. Some individuals have neurological problems, such as hemiplegia, or may have obstruction of blood flow in the brain or abnormal bleeding in the brain, which can lead to stroke. People with AR-HIES have a higher than average risk of developing cancer, especially hematological malignancies or skin.
Generally, this process is due to mutations in the gene DOCK8, located on the short arm of chromosome 9 (9p24.3). This gene encodes a protein that plays a critical role in the survival and function of various cell types of the immune system. One function of the protein is to help maintain the structure and integrity of immune T cells and NK cells, which recognize and attack foreign invaders. In addition, protein DOCK8 is involved in chemical signaling pathways that stimulate immune B cells to mature and produce antibodies.
They have identified at least 113 mutations in the gene DOCK8 in people with hyper-IgE syndrome autosomal recessive (AR-HIES). The mutations described so far have been: nonsense mutations (5), and cutting mutations -splicing- binding (5), small deletions (3), major deletions (14), and complex rearrangements (1). DOCK8 gene mutations result in little or no coding DOCK8 functional protein. The deficiency of this protein affects the normal development and function of immune cells. It is believed that NK cells and T cells lacking DOCK8 can not maintain their shape as they move through dense, such as those found inside the skin spaces. Abnormal cells die, which results in decreasing the number of cells. A deficiency of these immune cells affects wing response against foreign invaders, leading to frequent in individuals with AR-HIES serious viral infections of the skin. The absence of DOCK8 also impairs the maturation of B cells and antibody production. The lack of this type of immune response leads to recurrent infections of the airways in people with the disease. It is unclear how gene mutations are involved in DOCK8 other features of AR-HIES, such as elevated levels of IgE, autoimmunity and neurological problems. Some people with AR-HIES do not have mutations in the gene DOCK8. The genetic cause of the disease in these individuals is unknown.
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 in IVAMI: in IVAMI perform detection of mutations associated with hyper-IgE syndrome autosomal recessive, by complete PCR amplification of the gene exons DOCK8, 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).