Giant congenital melanocytic nevi (melanocytic nevi Giant congenital) - Genes NRAS or BRAF.
Congenital melanocytic nevus giant is a skin disease characterized by a patch of dark skin consisting of melanocytes. It is present at birth or shortly after birth. In newborns nevi may be small, but usually grows along the body grows and eventually could be at least 40 cm wide. The nevus can appear anywhere on the body, but most commonly found on the trunk or limbs. The color varies from brown to black and can become darker or lighter over time. The surface may be flat nevus, rough, raised, thick, or full of voids. Furthermore the surface may vary in different regions of the nevus, and can change over time. Often the skin nevi is dry and prone to dermatitis. Similarly, hypertrichosis may occur in the area of nevus. People with congenital melanocytic nevus giant may have more than one nevus. Often the other nevi are smaller than the giant nevus. Affected individuals may have one or two additional nevus or nevi multiple small extending on the skin known as nevi or broadcast satellites.
Affected people may feel anxious or emotional stress because of the impact that nevus can have on your appearance and your health. Affected children may develop emotional or behavioral problems. Some affected individuals develop neurocutaneous melanosis. These melanocytes may be distributed or grouped in clusters. Its growth can cause increased pressure in the brain, leading to headaches, vomiting problems, irritability, seizures and movement. Furthermore, brain tumors can develop. People with congenital melanocytic nevus giant have between 5% to 10% higher risk of developing melanoma. Melanoma usually begins in the nevus, but can develop when melanocytes invade other tissues, such as brain and spinal cord, become cancerous. When melanoma occurs in people with congenital melanocytic nevus giant, the survival rate is low. Other types of tumors can also develop in people with congenital melanocytic nevus giant, including sarcomas, lipomas and schwannomas.
In most cases, this process is due to mutations in the gene NRAS. Rarely, mutations in the BRAF gene are also responsible for this disease.
The NRAS gene, located on the short arm of chromosome 1 (1p13.2), encodes a protein called N-Ras which is mainly involved in regulating cell division. Through signal transduction, protein transmits signals from outside the cell to the cell nucleus. These signals instruct the cell to grow and proliferate, differentiate , or mature. The N-Ras protein is a GTPase, which means that converts GTP GDP molecule in the molecule. To transmit signals, the N-Ras protein must be activated by binding with a GTP molecule. The N-Ras protein is inactive when converted GTP to GDP. When the protein is bound to GDP, it does not relay signals to the cell nucleus. The NRAS gene belongs to a class of genes known as oncogenes. When they are mutated oncogenes have the potential to cause normal cells to become cancerous. They have identified at least 2 mutations in the NRAS gene in people with congenital melanocytic nevus giant. These mutations replace the amino acid glutamine, either by lysine or arginine, at position 61 of the protein (Q61K Gln61Lys or and Gln61Arg or Q61R). These mutations lead to the production of a N-Ras constitutively active protein. Instead of triggering cell growth in response to particular signals out of the cell, overactive protein directs cells to grow and divide constantly. Uncontrolled cell growth of melanocytes leading to the first large patch of dark skin pigmentation characteristic of giant congenital melanocytic nevus. Uncontrolled cell growth of melanocytes after birth contributes to the risk of developing melanoma in affected individuals.
The BRAF gene, located on the long arm of chromosome 7 (7q34), encodes a protein that 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. The mutation identified in the BRAF gene responsible congenital giant melanocytic nevus, V600E, leads to encoding an abnormally active protein, which interrupts the regulation of growth and cell division. Unregulated cell growth of the first melanocytes leads to the characteristic skin patch darkly pigmented nevus giant congenital melanocytic. Uncontrolled cell growth of melanocytes after birth contributes to the risk of developing melanoma in people affected.
This disease usually not inherited but arises from a mutation in the body cells that occurs after conception. This alteration is called a somatic mutation. A somatic mutation in a copy of NRAS or BRAF gene is sufficient to express the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with congenital giant melanocytic nevus, by complete PCR amplification of exons NRAS or BRAF of 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).