Anhidrotic ectodermal dysplasia with immunodeficiency (anhidrotic ectodermal dysplasia With immunedeficiency) - Genes and NFKBIA IKBKG.
The anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) belongs to a group of disorders called ectodermal dysplasias characterized by an abnormal development of ectodermal tissues including skin glands, hair, teeth and sweat glands. Signs and symptoms of EDA-ID are apparent shortly after birth and include skin abnormalities such as areas that are dry, wrinkled or darker than the surrounding skin color, thinning hair on the scalp and hipotricosis, Hypodontia or teeth small and pointed and hipohidrosis because they have fewer sweat glands than normal or your sweat glands do not function properly. Anhidrosis can cause hyperthermia, especially in hot weather.
Immune deficiency EDA-ID varies among those affected. Often, people with the disease encode abnormally low immunoglobulin concentrations, which makes it difficult for people to fight infection. In the EDA-ID, the T cells and B cells of the immune system have a reduced ability to recognize and respond to foreign invaders (such as bacteria, viruses and yeasts). Other key aspects of the immune system may also be affected, leading to recurrent infections. Often these people suffer from pneumonia, otitis media, sinusitis and lymphadenitis, and skin infections, bone and gastrointestinal tract. Approximately a quarter of the people with this disease have alterations involving abnormal inflammation, such as inflammatory bowel disease or rheumatoid arthritis. The life expectancy of affected individuals depends on the severity of immune deficiency, but most people do not live beyond infancy.
This disease is due to mutations in genes IKBKG, located on the long arm of the X (Xq28) and NFKBIA chromosome, located on the long arm of chromosome 14 (14q13). These genes encode protein subunits IKK complex, which is a group of related proteins that regulates the activity of the kappa-B-nuclear factor. The nuclear factor kappa-B is a complex of proteins that bind DNA and control the activity of other genes, including genes that direct the body 's immune response and inflammatory reactions. It also protects cells from certain signals that would otherwise cause apoptosis.
There are more than 20 mutations in the gene IKBKG and at least 5 mutations in the gene NFKBIA, in people with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). Mutations in these genes result in encoding proteins with altered function, thereby reducing the activation of kappa-B-nuclear factor. These changes alter certain signaling pathways within immune cells, which results in immune deficiency. It is unclear how mutations in these genes alter the development of skin, teeth, sweat glands and other tissues, although it is probably due to abnormal signaling-kappa-B nuclear in other cell types factor. The severity of the signs and symptoms depends on the level of impaired protein function. A higher level of protein function is associated with milder disease.
When the disease is due to mutations in the gene IKBKG is inherited with a recessive X - linked pattern in males, an altered copy of the gene in each cell is sufficient to cause disease. In women, a mutation would have to happen in both copies of the gene to cause the disease. Because it is unlikely that women have two copies of the altered gene IKBKG, males are affected by X - linked recessive disorders much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. On the other hand, when the disease is due to mutations in the NFKBIA gene is inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to cause disease. Most cases are due to new mutations in the gene and occur in people with no history of disease in your family.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), by complete PCR amplification of the exons of IKBKG and NFKBIA, respectively, and subsequent sequencing genes.
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).