Antithrombin, hereditary deficiency ... (Hereditary antithrombin deficiency) - Gen SERPINC1.

Hereditary antithrombin deficiency is a disorder of blood clotting. People with this disorder have a higher risk of developing abnormal blood clots, especially in the deep veins of the legs causing deep vein thrombosis (DVT). Affected individuals also have a higher risk of pulmonary embolism (PE). In hereditary antithrombin deficiency, abnormal blood clots usually form only in the veins, although rarely can occur in arteries. About half of those affected by the disease develop at least an abnormal blood clot throughout his life, which usually develop after adolescence.

Other factors that may increase the risk of abnormal blood clots in people affected include advanced age, surgery or immobility. The combination of hereditary antithrombin deficiency and other inherited blood clotting disorders may also influence risk. Affected women have an increased risk of developing an abnormal blood clot during pregnancy or shortly after birth. They may also have an increased risk of miscarriage or stillbirth.

This process is due to mutations in the gene SERPINC1, located on the long arm of chromosome 1 (1q25.1). This gene encodes a protein called antithrombin (formerly known as antithrombin III), one type of serine protease inhibitor (serpin) which helps to control various types of chemical reactions by blocking the activity of certain proteins. Antithrombin in the bloodstream and is important in controlling blood clotting. Specifically, antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin.

They have identified at least 220 mutations in the gene that result SERPINC1 hereditary antithrombin deficiency. Most mutations change the amino acids in antithrombin, which prevents control blood clotting. Affected individuals do not have enough functional antithrombin to inactivate coagulation proteins, which leads to increased risk of developing abnormal blood clots. Hereditary antithrombin deficiency can be divided into type I and type II on the basis of the mutation in the gene SERPINC1. Type I is due to mutations that prevent cell encoding antithrombin. Individuals with this type have only a functional copy of the gene in every cell SERPINC1, resulting in approximately half the normal amount of antithrombin. Mutations that cause type II coding result of altered antithrombin protein with reduced activity. People with this form of the disease usually have normal levels of antithrombin, but the protein does not work properly. Type II, can be further subdivided depending on whether the mutation affects binding to thrombin and other coagulation factors (type IIa), heparin (type IIb), or both (IIc type). Individuals with an inherited deficiency of antithrombin type IIb have a lower risk of formation of an abnormal blood clot that persons with other forms, because the antithrombin protein is capable of inactivating coagulation proteins without heparin.

Hereditary antithrombin deficiency typically inherited in an autosomal dominant pattern, meaning that an altered copy of the gene in every cell SERPINC1 is sufficient to result in the alteration. Altered inherit two copies of the gene in each cell is generally incompatible with life. However, they described some people seriously with mutations in both copies of the gene in every cell SERPINC1.

Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary antithrombin deficiency, by complete PCR amplification of the gene exons SERPINC1, 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).