Pilot Study of Preconception Carrier Screening in Russia: Initial Findings and Challenges

<b>Background/Objectives</b>: This study reports on findings from the first preconception screening performed in Russia and provides a comprehensive discussion of the significant results and challenges faced during the implementation of the project. <b>Methods</b>: Using a targeted sequencing panel of 33 genes (associated with 29 autosomal recessive and 4 X-linked diseases), we analyzed 165 couples considering pregnancy. The screening design also included analysis of the frequent pathogenic variants in the <i>SMN1</i>, <i>DMD</i>, <i>CFTR</i>, and <i>CYP21A2</i> genes that may not be detected through the next-generation sequencing approach. The sequential screening protocol, wherein the female partner was tested first, was used. <b>Results</b>: The results revealed that 35.8% of women (<i>n</i> = 59) were carriers of at least one pathogenic or likely pathogenic (P/LP) variant, with 7.9% of women (<i>n</i> = 13) carrying variants in two or more genes. Notably, the analysis identified 5 deletions of exon 7 in the <i>SMN1</i> gene, 1 deletion of the <i>CYP21A2</i> gene, and 1 large duplication in the <i>DMD</i> gene in female participants. The most frequently identified pathogenic variants occurred in the <i>CYP21A2</i>, <i>GJB2</i>, <i>SERPINA1</i>, and <i>ATP7B</i> genes. The screening identified six couples (3.6% of the cohort) at high risk of having a child with an autosomal recessive or X-linked genetic disorder. <b>Conclusions</b>: This pilot study confirms the high clinical utility of the gene panel, effectively evaluating reproductive risk in couples without a known family history of monogenic diseases. The findings indicate that the observed frequencies of identified gene variants differ from those theoretically expected, with a notable percentage of identified couples being at relatively high risk. Furthermore, these results highlight the indispensable role of comprehensive genetic counseling both before and after testing to ensure an appropriate preconception testing algorithm and informed reproductive decision-making.