Other genetic tests

Thrombophilia is a tendency to increased blood clotting, which is influenced by both innate dispositions and external influences (e.g. exercise, weight, age, smoking, injury, medication). People with a higher blood clotting capacity are at greater risk of blood clots (thrombi), which can lead to partial or complete closure of blood vessels - most commonly the deep veins of the lower limbs (deep vein thrombosis). A part of the clot may break loose, travel through the venous system and close a pulmonary vessel after passing through the heart - resulting in a pulmonary embolism. Thrombosis of the placenta can threaten the course of pregnancy.

The external stimulus for the formation of blood clots may be hormonal contraception, hormonal treatment of infertility or the period of pregnancy, therefore the examination of the inherited component of thrombophilia belongs to the basic preconception genetic examination. The results of the testing influence the treatment of fertility disorders and the care of pregnant women. Knowledge of the innate disposition to blood clotting can help not only in the reproductive period of life, but also during surgery, long-term immobilization or
treatment of chronic diseases.

We are investigating two important alterations - thrombophilic mutations in the F5 and F2 genes, which affect the composition and function of two proteins (factor V and factor II) that are significantly involved in the blood clotting process:
- Leiden mutation (FV Leiden) of the gene for clotting factor V - a mutation at position 1691 in the F5 gene leads to a substitution of the amino acid arginine for glutamine at position 506 (R506Q) of this protein.
- Mutation of the gene for clotting factor II (F II prothrombin) - mutation at position 20210 of the F2 gene. The finding of the mutation indicates an increased innate disposition to blood clotting, and certain preventive measures must be implemented. In the Czech population, 5-10% of carriers of the FV Leiden mutation and 1-2% of carriers of the FII prothrombin mutation.

Thrombophilic mutations are transmitted from generation to generation. We recognize:

- heterozygotes: an individual who has inherited the mutation from only one parent; his or her liver produces a mixture of normal and altered clotting factor and has an increased risk of developing thrombosis,
- homozygotes: an individual who has inherited the same mutation from both parents; his/her liver produces only the more active clotting factor with a more pronounced effect and therefore has a very high risk of developing thrombosis.

It is an autosomal dominant inheritance; a heterozygote (carrier of one mutation) has a 50% risk of passing the mutation to his/her children regardless of their sex; a homozygote will always pass the mutation to his/her children.

The presence of an inherited thrombophilic mutation poses a 3-5 times higher risk of developing deep vein thrombosis compared to the general population, but this does not mean that every carrier will suffer from thrombosis. The development of thrombosis usually occurs only through the co-action of other acquired thrombophilic factors:
- age over 45 years,
- obesity, smoking, alcohol,
- atherosclerosis and other cardiovascular diseases,
- abdominal and orthopaedic surgery,
- trauma and long-term immobilisation,
- use of hormonal contraceptives or treatment with sex hormones (thrombophilic mutations are contraindicated in homozygotes),
- pregnancy and six months of childbirth,
- oncological diseases and their treatment,
- loss or insufficient fluid intake (dehydration),
- autoimmune diseases (e.g. antibodies to phospholipids),
- the presence of mutations in other genes associated with blood clotting.

If multiple thrombophilic factors come together, thrombosis can occur in anyone, but in individuals with congenital thrombophilia, minor external influences are sufficient to induce thrombosis.

Knowledge of genetic predispositions is a key element in preventing and minimizing problems associated with thrombosis. This information can be used to tailor a lifestyle - getting enough exercise, taking in adequate fluids, following a rational diet, maintaining an optimal body weight, not smoking. These basic measures can significantly reduce the risk of disease.

At the same time, haematological monitoring or therapy is provided in situations of risk - for example, during pregnancy. If medical interventions are necessary, the attending physician should always be informed of the tendency to increased blood clotting!

Cystic fibrosis is a serious and incurable inherited disease caused by mutations in the CFTR gene, which controls the activity of the chloride channel in the cell membrane. The disease affects many organs, especially the respiratory, digestive and reproductive systems. A thick mucus builds up in the patient's lungs and harbours bacteria, leading to repeated respiratory infections and permanent damage to the lungs. Patients also often have nutritional problems, as the pancreas does not properly produce digestive enzymes, and so they do not thrive and gain weight despite a high-calorie diet. Men are infertile, having no sperm present (azoospermia) due to the congenital absence of the vas deferens.

CF is an autosomal recessively inherited disease, which means that the presence of two mutations in a patient is necessary for the development of the disease - one mutation inherited from the mother, the other from the father. Therefore, the parents of the patient are healthy carriers of the mutation (disease susceptibility) and have a 25% chance of having a child with cystic fibrosis. In the Czech population, every 26th person carries a CFTR gene mutation!

The aim of genetic testing is to confirm or exclude mutations in the CFTR gene in the patient under examination. To date, there are about 1800 known mutations, the most common of which is the F508del mutation. Our test detects 50 CFTR gene mutations commonly found in the European population; their absence reduces the risk of carrying a CFTR gene mutation to 1 in 400. In the case of a proven mutation, molecular genetic testing of the wider family is recommended for the prevention of CF.

Cystic fibrosis is currently an incurable disease whose consequences can only be mitigated by early diagnosis. The only prevention against the birth of a child affected by CF is the use of assisted reproductive techniques with preimplantation diagnosis (PGD), where only genetically healthy embryos are selected for transfer into the uterus. If a woman becomes pregnant naturally, she can undergo prenatal diagnosis (genetic testing of the fetus in pregnancy) and if the fetus is found to be affected, the pregnancy can be terminated for genetic reasons.

Proof (or demonstration) of paternity is done by testing blood or other biological samples. Methods used in forensic science compare the genetic features stored in the DNA of the mother, the putative father and the offspring.

Paternity
- is proven with a probability of more than 99.9%
- is ruled out with 100% certainty.

Paternity test by agreement between the mother and the putative father:
- results cannot be used for legal acts!

Non-invasive paternity test by agreement from the 11th week of pregnancy:
- only the blood of the mother and the presumed father is examined,
- the test can only be performed in singleton pregnancies.