JBRA Assist. Reprod. 2025;29(Suppl 1):26-26
POSTER PRESENTATION
doi: 10.5935/1518-0557.20250080
1Igenomix part of Vitrolife, Brazil
2Igenomix part of Vitrolife, Argentina
3Igenomix part of Vitrolife, Spain
Objective: Carrier genetic testing (CGT) has been highly recommended for consanguineous couples as it can identify known pathogenic variants in recessive genes, allowing the detection of heterozygous mutations in healthy couples which would represent a 25% risk of having an affected child. Previous studies indicate that 2 to 3% of non-consanguineous couples are carriers of a pathogenic variant in heterozygosity in the same gene (Ricca et al., 2024; Martin et al. 2015). For consanguineous couples, studies indicating this frequency are scarce, however, this data is extremely relevant for family planning and pre-conception genetic carrier screening counseling. The aim of this study is to evaluate the frequency of increased risk for AR conditions in the offspring of consanguineous couples undergoing carrier genetic screening.
Methods: Retrospective study including 91 consanguineous couples, who underwent CGT at Igenomix Brazil between March 2020 and September 2024. DNA samples were obtained from blood or saliva of the patients and analyzed by Next Generation Sequencing (NGS) for over 2,000 genes associated with known AR and X-linked disorders (OMIM-based) included in the CGT Exome Igenomix carrier screening panel.
Results: Of the 91 consanguineous couples who underwent CGT, 38% couples (n=35/91) showed positive matching, indicating an increased risk for one or two recessive conditions. Among first cousins, the positive matching rate was 50% (n=17/34), while for secondand third-degree cousins the rate was 34% (n=10/29). When the degree of kinship was greater than third degree, no increased risk of recessive conditions in the offspring was observed (n=0/4) with this genetic panel. All the consanguineous couples together showed an increased reproductive risk for 37 different AR genes. Among these, 32 couples (92% of the positive matches) were carriers of the same variant in heterozygosity, which indicates a 25% risk of homozygosity in their offspring. Four couples (12%) had distinct variants in heterozygosity, which confers a 25% risk of compound heterozygosity in their offspring. The matching of 4.4% (n=4/91) couples indicated an increased risk for two different AR conditions.
Conclusion: The risk of positive matching, indicating high reproductive risk, in consanguineous couples, is significantly higher than that observed in unrelated couples (38% in this study vs 3% in Martin et al., 2015). This difference was expected due to the sharing of a large proportion of their genetic material. However, the frequency of positive matching was lower than in the study by Sallevelt et al. (2021), in which it was 56%. This difference may have occurred because one-quarter of the participants in this study already knew they had a high risk for at least one AR condition due to a family history. The presence of the same variant in both reproductive partners is a typical outcome in consanguineous couples, being observed in 92% of positive matches. It was observed that the higher the degree of kinship, the greater the risk of positive matching. The data collected in this study reinforce the importance of extended carrier panels in the family planning process of consanguineous couples and can assist in providing genetic counseling.
References
Martin J. et al. Fertil Steril. 2015;104:1286-93