Erdheim-Chester Disease ... (Erdheim-Chester disease) - Gen BRAF.

Disease Erdheim-Chester is a rare disorder characterized by histiocytosis, in which the immune system produces excessive amounts of histiocytes. Histiocytes usually work to destroy foreign substances and protecting the body against infection. This disease is classified as a form of non - Langerhans cell histiocytosis contradistinction to the Langerhans Cell Histiocytosis, consisting of the accumulation of a specific type of histiocito called Langerhans cells. In Erdheim-Chester disease, histiocytosis leads to an inflammation that can damage organs and tissues throughout the body, causing them to become thick and dense, causing fibrosis. This tissue damage can lead to organ failure.

Often, affected individuals have bone pain, especially in the legs and arms, because of osteosclerosis. Damage to the pituitary gland can lead to hormonal problems such as diabetes insipidus leads to excessive urination. Intracranial hypertension, caused by the accumulation of histiocytes in the brain can cause headaches, seizures, cognitive impairment, or problems with movement or sensation. Moreover, those affected may also have difficulty breathing, heart or kidney disease, exophthalmos, skin growths, or infertility. Similarly, these individuals may have fever, night sweats, fatigue, weakness and weight loss.

In general, the signs and symptoms of Erdheim-Chester disease appear between 40 and 60 years, although it can occur at any age. The severity of disease varies widely. While some affected individuals have little or no associated health problems, others have severe complications that can be life threatening.

This process is due to changes in the BRAF gene, located on the long arm of chromosome 7 (7q34). The protein encoded by this gene helps transmit chemical signals from outside the cell to the cell nucleus. This protein is part of a signaling pathway known as the RAS / MAPK pathway, which controls several important cellular functions. Specifically, the RAS / MAPK pathway regulates growth and proliferation, differentiation, migration and apoptosis. Chemical signaling through this pathway is essential for normal development before birth. The BRAF gene belongs to a class of genes known as oncogenes, meaning that a mutation in them has the potential to cause normal cells to become cancerous.

It has identified at least one mutation in the BRAF gene in some people with Erdheim-Chester disease. The identified mutation affects a single amino acid in BRAF. Specifically, the mutation replaces the amino acid valine for glutamic acid at amino acid position 600 (V600E or Val600Glu). This mutation leads to coding a BRAF protein is abnormally active, which alters the regulation of growth and cell division and can allow histiocytes grow and divide unchecked, leading to abnormal accumulation of histiocytes occurs in Erdheim-Chester disease.

The Erdheim-Chester disease is not inherited, but is due to a somatic mutation in histiocytes or their precursor cells during the life of an individual.

Tests in IVAMI: IVAMI performed in detecting mutations associated with disease Erdheim-Chester, by complete PCR amplification of the exons of the BRAF 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).