Protein S deficiency of ... (Protein S deficiency) - Gen PROS1.
The protein S deficiency is a disorder of blood coagulation. People with this disease have a higher risk of developing abnormal blood clots, so they have risk of forming thrombi that occurs in the deep veins of the arms or legs. If a thrombus dislodges deep through the bloodstream and lodges in the lungs, can cause pulmonary embolism (PE). Other factors that may increase the risk of blood clots in people with mild protein S deficiency include age, surgery, immobilization or pregnancy. The combination of protein S deficiency and other inherited disorders of blood clotting can also influence risk. However, many people with mild protein S deficiency never develop an abnormal clot. In severe cases of protein S deficiency, children develop a disturbance of blood clotting shortly after birth, threatening, called withering purple. This alteration is characterized by the formation of clots in the small blood vessels throughout the body. These clots disrupt the normal flow of blood and may cause necrosis. Widespread blood clotting consume all available blood proteins. As a result, abnormal bleeding occurs in various parts of the body. People who survive the neonatal period may experience recurrent episodes of fulminant purpura.
This process is due to mutations in the gene PROS1, located on the long arm of chromosome 3 (3q11.2). This gene encodes the S protein, found in the bloodstream and it is important to control blood clotting. By itself, the S protein can not carry out the chemical reactions necessary for the regulation of the formation of blood clots. Instead, the S protein binds to certain enzymes and improves function. Based on this action, the S protein is a cofactor for activated protein C enzyme (APC). This enzyme inactivates some of the blood clotting proteins (Va and factor VIIIa factor). S protein also helps an enzyme, known as an inhibitor of tissue factor pathway (TFPI), to block the activity of another protein coagulation factor Xa.
There are more than 220 mutations in the gene PROS1 causing protein S deficiency Most of these mutations change the amino acids in protein S, which prevents acting as a cofactor. The protein S deficiency can be divided into types I, II and III on the basis of how mutations in the gene PROS1 affect protein S. Type I is caused by genetic mutations that lead reduced concentrations of protein S, which It is causing the increased risk of formation of abnormal blood clots. Mutations causing type II results in the production of an altered protein S with reduced activity. Individuals with type II disease have normal levels of protein S, but the protein is not able to interact with other molecules involved in blood clotting. Type III occurs when there is a low amount of free protein S, but the total amount of protein S is normal. Since free protein S that is a protein S bound more effective cofactor, reduced levels of free protein S can interrupt the inactivation of blood coagulation proteins.
The protein S deficiency is inherited as an autosomal dominant, which means that an altered copy of the gene in each cell is sufficient to cause the alteration. Individuals who inherit two copies of the gene altered in every cell have severe deficiency of protein S.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with protein S deficiency, by complete PCR amplification of exons PROS1 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).