In the Czech Republic, genetic testing for inborn errors of immunity (IEI) is primarily conducted at specialized academic/ university hospital laboratories. The main institutions performing these tests are the Molecular Genetic Laboratory, affiliated with the Centre of Cardiovascular Surgery and Transplantation and the Medical Faculty of Masaryk University in Brno, and, to a lesser extent, the Laboratory of Molecular Genetics, Childhood Leukaemia Investigation Prague, at the University Hospital Motol in Prague. These laboratories work closely with one another, as well as with clinical immunologists and geneticists, to ensure accurate analysis and interpretation of test results.
Genetic testing for IEI is typically recommended by an immunologist, who then refers the patient to a medical geneticist. The medical geneticist is responsible for conducting genetic counselling, both pre-test and post-test, prescribing and selecting the appropriate genetic test, and evaluating the results in the context of family history. The genetic counselling process ensures that patients and their families understand the implications of genetic testing and its potential outcomes.
Genetic counselling and testing for IEI are fully covered by public health insurance (PHI) when indicated and with the patient’s informed consent. PHI is mandatory for Czech citizens, with coverage provided by the state for children and retired individuals. However, PHI only covers germline next-generation sequencing (NGS) testing once per person in a lifetime, regardless of the medical indication.
For registered refugees from Ukraine, PHI is provided by the Czech Republic. It covers full healthcare, meaning that their IEI genetic tests are also covered. However, other refugees without health insurance generally need a sponsor to undergo genetic testing.
NGS testing in the Czech Republic is conducted primarily through targeted panels and/or whole exome sequencing (WES). Recently, there has been a shift towards WES enriched with probes specific for IEI-related genes, allowing for better detection of specific IEIs sequences that might be missed by standard WES panels, such as those involving intronic or UTR sequences. This approach also facilitates a more comprehensive evaluation of CNVs in IEI-related genes. Since PHI only covers NGS testing once in a life per person, performing WES ensures that future genetic issues can be examined without requiring additional sequencing.
NGS test results are analysed and interpreted by genetic laboratories in close collaboration with immunologists and geneticists to ensure precise evaluation and clinical interpretation. Detected variants are classified based on their pathogenicity, and all findings in a patient’s case are then evaluated to determine whether they are disease-causing, disease-associated, pathogenic but not related to the patient’s phenotype, or variants of uncertain significance (VUS). Once the analysis is complete, the laboratory report is sent to the submitting geneticist and immunologist.
The median waiting time for IEI genetic test results in the Czech Republic is approximately four months, with a maximum waiting time of up to nine months. However, in cases requiring urgent testing, expedited processing is performed, with results available within two to four weeks.
Genetic testing services are available to patients from all regions, with clinical immunologists referring patients to geneticists for evaluation. Once a specific IEI diagnosis is established, patients typically receive ongoing follow-up care primarily in specialised Clinical Immunology departments at University hospitals in Prague, Brno, Hradec Králové, Olomouc, and Plzeň. Specialists in these centres can arrange functional testing available within the Czech Republic or through collaboration within ERN RITA or ESID.
Newborn screening for severe combined immunodeficiency (SCID) and agammaglobulinemia using TREC and KREC testing was implemented as a mandatory part of neonatal screening in January 2024, following the successful completion of a two-year pilot project. Two national centres, located in Prague and Brno, manage the screening process. Positive results are reported to IEI specialists at the University Hospitals in Prague and Brno. If IEI is suspected, the molecular genetic examination is then conducted.
Hana Grombirikova & Tomas Freiberger
