Preconceptional Carrier Screening

What is preconceptional carrier screening?

Preconceptional Carrier Screening is a genetic screening easily performed in a blood sample that allows to determine the risk of the couple of having a child with single gene disorder.

The test can screen more than 32.000 causal mutations encompassing to more than 360 genetic diseases that are inherited in:

  • Autosomal Recessive pattern: two copies of an abnormal gene must be present in an individual to be affected of the disease. This means that the individual inherited one abnormal copy of the gene from each parent. The parents don’t suffer from the disease but are carriers and can transmit it to their future children. The risk of having an affected child when both members of the couple are healthy carriers of the same genetic condition is 25%.
  • X-linked pattern: X-linked diseases are caused by mutations in genes located on chromosome X. Females have two chromosomes X while male have one chromosome X and one chromosome Y. In X-linked recessive conditions, males with the mutated chromosome X are affected and carrier females (one copy of the mutation) don’t usually express the phenotype. Every son from a carrier woman has a 50% chance of inheriting the defective gene and therefore developing the disease. Each of the daughters will have a 50% chance of inheriting the defective gene and being carriers of the disease. Affected men will transmit the mutation to all their daughters and none of their sons.
  • (e.g. Hemophilia, Duchenne Muscular Dystrophy). In X-linked dominant condition, women and men that only have one mutated X can be affected. Both sons and daughters of an affected mother have a 50% chance of being affected. Affected fathers transmit the disease to all their daughters (affected) but none of their sons (e.g. Fragile X syndrome).

The test covers the most serious and common autosomal recessive and X-linked diseases, including Cystic Fibrosis, Sickle-Cell Anemia, Thalassemia, Spinal Muscular Atrophy and Fragile X syndrome. Each disease and mutation is meticulously selected based on carrier rate, clinical severity and availability of reproductive and treatment options.

The analysis is performed by NGS although some diseases are performed by other technologies as Fragile-X (TP-PCR technique) or Spinal muscular atrophy and Duchenne muscular dystrophy (MLPA technology).

How is it performed?

  1. A blood sample is extracted from one or both members of the couple that want to proceed with the test. Previous genetic counseling and fully information about the test is provided to the couple.
  2. Samples are tested and a report is issued after 2-3 weeks including all the mutations identified (if any). The report is summited to the couple or its referral doctor. Post-test genetic counselling is provided.
  3. It is recommended to offer the test to both members of the couple. If only one partner is initially tested and he/she is identified as a carrier of a genetic disease, the partner should be tested for this particular disease to assess the risks for their future offspring. Additionally, immediate family members of a carrier person are at risk of being carriers as well. Genetic testing to other family members is advisable.

Who can benefit?

The test is for any marriage who was planning to create a family and wants to know their risks of transmitting a genetic condition to their offspring. Everybody is an unknowing carrier of one or multiple mutations that can cause genetic disorders. Although to be a carrier of a genetic disease has not usually implications on your health, when both members of the couple are carriers of the same recessive genetic disorder, the risk to have affected children is as high as 25%.

Consanguineous marriages (e.g. first-degree cousins) are at higher risk of being both carriers of the same recessive genetic condition due to mutations inherited from a common ancestor. Thus, Preconceptional Carrier Screening can be very valuable tool for them.

Preconceptional Carrier Screening allows us to identify these couples and counsel them about their options to conceive a non-affected child. One of their choices it is Preimplantational Genetic Diagnosis (PGD), that allows to test the embryos in an IVF cycle for the specific disease before they are transferred to the maternal uterus.

The test covers the most serious and common world-wide autosomal recessive and X-linked diseases. However, in case the results turn negative, there is always a residual risk that partners were carriers of another rare and infrequent genetic disease not included in the test. Genetic counselling is provided to couples before requesting the test and when the results are reported.