Lekárska genetika a diagnostika 1/2024
Occurrence of causal DNA variants associated with SCID congenital immune disorders in the Slovak population
Purpose: Severe combined immunodeficiencies (SCID), belong to the group of inborn errors of immunity (IEI), and represent a heterogeneous set of diseases generally characterised by recurrent infections and manifestations of immune deregulation. The primary symptoms of the SCID are manifested preferentially in early childhood, and in the case of failed early treatment by bone marrow transplantation, it can be fatal, for the patient. The International Union of Immunological Societies (IUIS) has described overall 19 genes associated with SCID. Patients and methods: Our study has been focusing on molecular analysis of genes associated with SCID in the Slovak population. Samples of patients with the suspected IEI have been included in the study and further analysed by massive parallel sequencing, especially by virtual panel of IEI-associated genes, using CES or WES approaches. Samples were collected from Ambulances of Clinical Genetics from different regions of Slovakia in the period of 2019 to 2023. Results: In the cohort of 135 samples of patients with suspected IEI, we have identified overall 14 particular causal DNA variants with potential pathogenic and uncertain significance impact in genes associated with SCID. Altogether we have described two causal and one potentially causal DNA variant, associated with the SCID phenotype, exactly in the IL2RG and RAC2 genes. All causal variants have been classified into pathogenicity class 3/4 and 4, while we have not identified any variant of class 5. Conclusion: Our presented study has been focused on the comprehensive genomic analysis of SCID patients and described the relevant DNA variants, while represents a pilot study in the Slovak population. These findings confirm that the performance of the diagnostic approach by massive parallel sequencing in patients with IEI, represents a comprehensive approach, which leads to accelerated and effective diagnostics and further treatment.
Keywords: causal DNA variants, massive parallel sequencing, inborn errors of immunity (IEI), SCID, X-SCID
