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Genetics

You may find comprehensive information and indication about the genetic tests below performed by GenoID:

Detection of microdeletions (AZFa, AZFb, AZFc) of Y chromosome

A genetic damage affecting the azoospermia factor region (AZF) of Y chromosome is in the background of approx. 20% of idiopathic cases of oligo- azoospermia and of approx. 10% of all cases of oligo- and azoospermia. The extent of microdeletion has therapeutic and prognostic impacts. In case of confirmed microdeletion there is a possibility to enrol the patient into an in vitro fertilization program based on ICSI technology and cryopreservation of sperm collected at young age is recommended for future use for IVF. In case of successful ICSI microdeletions will be inherited by the male offspring. This test is recommended in case of both oligospermia and azoospermia.

Detection of number abnormalities of sex chromosomes (X, Y chromosome Aneuploidia)

In infertile men chromosome abnormalities can be detected at higher rates compared to the average population and the incidence is inversely proportional to the sperm count. Chromosomal factor participates in this process in the average of 5% of infertile men. This rate is up to 15% in men with azoospermia mostly comprising number or structural abnormalities of sex chromosomes. From aneuploidia of sex chromosomes the most common ones include Klinefelter syndrome (47, XXY) and at lower rate the 47, XYY and 45, X caryotype or the mosaic form thereof is in the background of infertility. The molecular genetic test for detection of aneuploidia of sex chromosomes can be used as a more rapid alternative to the long cytogenetic analysis or as a preliminary screening.

Analysis of F508, IVS5T/7T/9T, R117H, N1303K and G542X mutations of cystic fibrosis (CFTR) gene

Mutations of cytsic fibrosis (CF) disease represent relatively common causes of infertility in men. Some minor defects of CF gene do not cause typical cystic fibrosis but lead to infertility in men via congenital bilateral obstruction of the spermatic duct. Bilateral lack of the spermatic duct is accounted for 1-2% of infertility in men and majority of cases are caused by the defect of CF gene. In such case either a copy of CF gene contains a classical “serious” mutation – most often ΔF508 – and the other copy contains a so called „mild” mutation (e.g. R117H or IVS8-5T) or both copies carry „mild” mutations. This test is recommended for patients with azoospermia only.

Analysis of Leiden mutation of Factor V

It is indicated for deep vein thrombosis if the DVT of the upper limb occurs below 55 years of age; in case of DVT occurred at an unusual site (not in the lower limb) in any age; if possibility of familiar thrombophilia is present based on the family history. In case of all acquired factors increasing the tendency to thrombosis (pregnancy, major surgery, immobilization, women taking contraceptives, etc.) if the individual has already had thrombosis or there is the possibility of familiar thrombophilia is present based on the family history; or in case of a positive APC-resistance test.

Analysis of G20210A mutation of prothrombin gene

It is intended for susceptibility to both venous and arterial thrombosis. There is higher incidence of mutation than the average in patients with cerebral thrombosis. In women carrying the heterozygote form of the mutation the risk of myocardial infarction was at least 4 times higher then in those not carrying this mutation. Some studies have shown that mutation – particularly its homozygote form - may contribute to repeated abortions.

Analysis of C677T point mutation of ethylene tetrahydrofolate reductase (MTHFR) gene

Elevated blood homocysteine concentration (hyperhomocysteinaemia) as an independent factor increases the environmental and congenital risk ishceamic heart diseases, cerebrovascular diseases, peripheral atherosclerosis, deep vein thrombosis and foetal anencephalia. The most common congenital factors include point mutation (C677T) of ethylene tetrahydrofolate reductase (MTHFR) gene increasing the severity of hyperhomocysteinaemia. Patients carrying mutations increasing the tendency to have hyperhomocysteinaemia may reduce blood homocysteine levels by increased folic acid intake.

Analysis of polymorphism of ACE insertion/deletion

D variant carries increased risk of cardiovascular disease; I/I genotype patients respond better to ACE inhibitors and this genotype is related to the enduring physical performance as well.

Indications for testing:

  • increased risk for cardiovascular disease (presence of classical risk factors, positive family history)
  • stroke at a young age
  • before treatment of hypertension
  • to judge development potential in endurance sports athletes

 

Analysis of C282Y and H63D point mutations of haemochromatosis (HFE) gene

Haemochromatosis is a disease of iron metabolism with autosomal recessive pathway of inheritance in which iron is continuously absorbed and accumulated in various organs finally leading to irreversible tissue damages. It affects primarily the liver (cirrhosis, hepatocellular carcinoma), pancreas (diabetes mellitus), joints (arthralgia, arthritis) and heart (cardiomyopathy). The test is recommended in case of elevated transferring saturation and/or elevated ferritin levels if there is the clinical possibility of haemochromatosis; or in family members of homozygote patients even without clinical symptoms or laboratory results indicating haemochromatosis.

 

Familial breast and ovarian cancer
Analysis of 5 common mutations of BRCA1, BRCA2 genes

According to the international guidelines analysis of mutation of BRCA1 and -2 genes is indicated in case of presence of any of the following criteria: bilateral breast cancer; multiple breast cancer; breast AND ovarian cancer; breast cancer in men; first grade relative of a patient with any of the 4 diagnoses listed above; breast cancer below 40 years of age; >1 relative with breast AND >1 relative with ovarian cancer in one family branch; >3 relatives with breast or ovarian cancer in one family branch, in several generations; a relative with a confirmed mutation.

 

Paternity and relationship testing

Testing starts with the isolation of DNA from the submitted samples. The DNA samples are then subjected to examination of 15 selected sites that show variability in length in the population.  These 15 DNA fragments, with 2 copies each, make up a length pattern (profile) that is virtually unique to every person. In parent-child relationships, however, one copy of each fragment is identical by inheritance. In paternity testing, testing the mother helps to identify the paternal copies thus making testing more accurate. For the statistical calculations of the probability of paternity the frequencies of each length variation in the relevant population are considered. In most trio cases the probability of paternity either reaches 99.99% or is virtually zero. In motherless cases the number is, rarely, slightly lower.