Detection of G20210 A mutation in Prothrombin gene – factor II
The test consists in detecting the presence of G20210A mutation in the blood coagulation system gene, factor II – prothrombin.
The presence of 20210G>A mutation in the prothrombin gene is associated with the increased risk of thromboembolic disease, spontaneous miscarriages and other pregnancy pathologies (intrauterine deaths). Prothrombin is a proenzyme, precursor of thrombin, converting fibrinogen into fibrin (main component of a blood clot). A gene encoding factor II of the blood coagulation system is located on chromosome 11 (11p11-q12). The mutation consisting in replacing the nucleotide guanine with adenine at position 20210 of exon 14 of the prothrombin gene causes 20% increase of this protein level in plasma. This contributes to the increased activity of the blood coagulation system. The 20210G>A mutation is inherited in an autosomal dominant manner, and its incidence in the Caucasian population is estimated at approx. 2-3%. The carriers of one mutant copy of the gene demonstrate approx. 2-3-fold increase in the incidence of thromboembolic disease.
Detection of Leiden mutation in proaccelerin gene – factor V
The test consists in detecting the presence of G1619A [p.Arg506Gln] mutation in the blood coagulation system gene, factor V – proaccelerin.
. Factor V belongs to proteins involved in blood clotting process. Autosomal dominant factor V mutation, also referred to as Leiden mutation, is one of the most frequent genetic causes of thromboembolic diseases. It also results in the increased risk of spontaneous miscarriages and other pregnancy pathologies (intrauterine fetal death in the third trimester). The gene encoding factor V is located on chromosome 1 (1q21-q25). Replacing guanine G nucleotide with adenine A at position 1691 of exon 10 of the Factor V gene of the blood coagulation system results in the formation of the Leiden variant of this protein. The Leiden variant of proaccelerin does not undergo degradation by protein C (APC), leading to the increase in the plasma thrombin and then fibrin level, thus causing the increased risk of thrombosis. The incidence of this mutation in the Caucasian population is 2-13%. Carrying one copy of the mutant gene causes 5-10 fold increase in the disease risk, and in the event of carrying both mutant copies of the proaccelerin this risk increases 30-140 fold.
Detection of 2 mutations in CFTR gene
This test consists in the analysis of basic mutations in the CFTR gene.
It covers two changes within the CFTR gene which are most common in the Polish population: delF508 and dele 2,3, accounting for approx. 60% of all mutations. Mutations in the CFTR gene are a cause of cystic fibrosis. The CFTR gene is located on chromosome 7 and encodes a membrane protein that forms a chloride channel. Cystic fibrosis is one of the most common genetic disorders that is inherited in a recessive autosomal pattern. In the Polish population its incidence is 1 per 2500 of births. A broad spectrum of symptoms of cystic fibrosis is caused by the production of abnormally viscous mucus in all body organs with mucous glands. This leads to changes mainly in respiratory, digestive and reproductive system. Changes in the reproductive system cause bilateral absence or obstruction of vasa deferentia (CAVD, Congenital Absence of the Vas Deferens) in men, while in women they cause an increase in the density of cervical mucus, thereby hindering migration of the sperm. It is estimated that in Poland approximately 1.5 million people are asymptomatic carriers of mutations in the CFTR gene. Therefore a positive result of the test for CFTR in one of the partners indicates the need to test the other one. Determination who is the carrier of a disease in a given couple allows to estimate the risk of having a sick child.
Detection of polymorphism in MTHFR gene
This test allows to determine the methylenetetrahydrofolate reductase gene C677T polymorphism.
Methylenetetrahydrofolate reductase is an enzyme participating in the metabolism of folic acid and homocysteine. The MTHFR gene C677T polymorphism is related to the reduced activity and stability of the enzyme methylenetetrahydrofolate reductase (MTHFR). This leads to the blood serum homocysteine increase, in particular in cases of a diet poor in folic acid. Hyperhomocysteinemia (>15nmol/mL) is considered a risk factor for cardiovascular diseases (thrombosis, ischemic heart disease, atherosclerosis, stroke), neurodegenerative diseases, complications of pregnancy (recurrent miscarriages, neural tube defects) and numerous cancers. Change in MTHFR gene consists in C to T substitution at position 677 of exon 4, leading to substitution of amino acid alanine by valine in the enzyme molecule. Three polymorphisms of the MTHFR gene have been identified: T/T, C/T and C/C, with the incidence in the Caucasian population amounting to 8%, 40% and 52%, respectively. Carrying the T/T and C/T variants is related to reduced activity and stability of the MTHFR enzyme. Carriers of both TT gene copies demonstrate the lowest activity of the MTHFR enzyme (decrease in activity by up to 30%) and 25% increase in blood serum homocysteine. The risk of disease in these individuals increases 2-3 fold. Women with MTHFR C677T polymorphism (TT) are recommended to take folic acid already before the period of planned pregnancy or as soon as possible after the pregnancy has been diagnosed (5 mg daily per os and 25 mg of vitamin B6) and continue during pregnancy.