X - linked hyper IgM syndrome ... (X - linked hyper IgM syndrome) - Gen CD40LG.

Hyper IgM syndrome X - linked is a disease that affects the immune system and occurs almost exclusively in males. People with this disorder have abnormal levels of antibodies or immunoglobulins. There are several kinds of antibodies, and each has a different function in the immune system. Although the name of this disease means that people affected always have high levels of immunoglobulin M (IgM), some people have normal levels of this antibody. People with hyper IgM syndrome of X - linked have low levels of three other classes of antibody: immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin E (IgE). Deficiency of certain kinds of antibodies makes it difficult for people to fight infection.

Individuals with hyper IgM syndrome of X - linked begin to develop frequent infections in infancy and early childhood. The most common infections include pneumonia, sinusitis and otitis. Often, infections cause these children have chronic diarrhea and growth retardation. Some people with hyper IgM syndrome of X - linked neutropenia present. Affected individuals may develop autoimmune disorders, neurological complications of brain and central nervous system infections, liver disease and gastrointestinal tumors. These individuals have an increased risk of lymphoma. The severity of the disease varies among affected individuals, even among members of the same family. If left untreated, the disease can cause death in childhood or adolescence.

This process is due to mutations in the gene CD40LG, located on the long arm of chromosome X (Xq26). This gene encodes a protein called CD40 ligand found on the surface of T cell CD40 ligand binds to the receptor protein CD40, found on the surface of B cells of the immune system. B cells are involved in encoding antibodies or immunoglobulins that help protect the body against infection. B cells are capable of maturing cells encoding immunoglobulin M (IgM) without any signals from other cells. For B cells mature into cells that produce antibodies of a different class, the CD40 receptor must interact with the CD40 ligand. When these two proteins are connected, they trigger a series of chemical signals that instruct the cell B to start encoding the immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin E (IgE). CD40 ligand protein is necessary for T cells interact with other cells of the immune system, and plays a key role in T cell differentiation

Have identified more than 150 mutations in the gene CD40LG giving rise to hyper IgM syndrome X - linked These mutations lead to the encoding of a CD40 ligand or inhibit abnormal encoding this protein. If CD40 ligand does not bind to its receptor on B cells, these cells can not produce IgG, IgA, or IgE. Mutations in the gene CD40LG also affect the ability of the T cell to differentiate and interact with cells of the immune system. People with hyper IgM syndrome of X - linked are more susceptible to infections because they do not have a properly functioning immune system.

This disease is inherited in a recessive X - linked pattern in males, an altered copy of the gene in each cell is sufficient to express the disease. In women, a mutation would have to happen in both copies of the gene for the disease to be expressed. Because it is unlikely that women have two altered copies of this gene, 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.

Tests in IVAMI: in IVAMI perform detection of mutations associated with hyper IgM syndrome X - linked, by complete PCR amplification of the exons of the gene CD40LG, 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).