Pulmonary veno-occlusive disease ... (veno-occlusive disease Pulmonary) - Gen EIF2AK4.
Pulmonary veno-occlusive disease (EVOP) is characterized by the obstruction of the blood vessels that carry blood from the lungs to the heart. Occlusion is due to an abnormal accumulation of fibrous tissue in the small veins of the lungs, which narrows vessels and affects blood flow. Because blood flow through the lungs is difficult, pulmonary arterial hypertension occurs.
Problems with blood flow also impair the transfer of oxygenated blood through the body, causing signs and symptoms of the disease. These signs and symptoms include shortness of breath, fatigue, dizziness, lethargy, difficulty breathing and persistent cough at bedtime. As the disease gets worse, those affected may have cyanosis, chest pains, fainting and pulmonary edema. Some features often seen in people with PVOD by a CT scan may include centrolobulillar opacification. The affected individuals also have an abnormal thickening of certain tissues in the lungs, as described septal lines. In addition, mediastinal lymph nodes are abnormally enlarged.
This disease can begin at any age, and blood flow problems worsen over time. Due to increased blood pressure in the pulmonary arteries, the heart has to work harder than normal to pump blood to the lungs, which can eventually generate a heart failure. Most people most affected with this disease do not live more than 2 years after diagnosis.
This process is mainly due to mutations in the gene EIF2AK4, located in the long arm of chromosome 15 (15q15.1). In a few cases, it may be mutations in other genes. Other possible causes of EVOP include viral infection and exposure to toxic chemicals, including certain drugs used in chemotherapy. The EIF2AK4 gene encodes a protein that helps direct the response of a cell to changes that may damage the cell. This protein is found in various body tissues including walls of blood vessels. The EIF2AK4 protein can activate another protein called alpha eIF2 (eIF2?), which helps protein coding control. When cells are stressed, for example, when the amino acid level is too low, EIF2AK4 active eIF2?. When enabled, eIF2? stimulates processes that reduce protein coding, which helps conserve amino acids. In addition, the activated protein can trigger eIF2? encoding certain proteins quye act as transcription factors. Transcription factors regulated by eIF2? control the activity of genes involved in the processes contributing to reduce pressure on the cell.
They have identified at least 22 EIF2AK4 gene mutations in individuals with pulmonary veno-occlusive disease. The identified mutations probably lead to a complete loss of functional protein. However, it is unclear how the absence of functional protein EIF2AK4 leads to abnormalities characteristics PVOD pulmonary veins.
When pulmonary veno - occlusive disease is-due to mutations in the EIF2AK4 gene is inherited in an autosomal recessive pattern, which means that 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. In contrast, when the disease is due to mutations in other genes, you may have an autosomal dominant inheritance, which means that a copy of the altered gene in each cell is sufficient for the disease to be expressed. In these cases, a parent of an affected person usually has an increase in blood pressure in the vessels of the lungs.
Tests in IVAMI: in IVAMI perform detection of mutations associated with veno-occlusive pulmonary disease by the complete PCR amplification of exons EIF2AK4 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).