Carrier screening in the Mexican Jewish community using a pan-ethnic expanded carrier screening NGS panel

Purpose: The Mexican Jewish community (MJC) is a previously uncharacterized, genetically isolated group composed of Ashkenazi and Sephardi-Mizrahi Jews who migrated in the early 1900s. We aimed to determine the heterozygote frequency of disease-causing variants in 302 genes in this population. Methods: We conducted a cross-sectional study of the MJC involving individuals representing Ashkenazi Jews, Sephardi-Mizrahi Jews, or mixed-ancestry Jews. We offered saliva-based preconception pan-ethnic expanded carrier screening, which examined 302 genes. We analyzed heterozygote frequencies of pathogenic/likely pathogenic variants and compared them with those in the Genome Aggregation Database (gnomAD). Results: We recruited 208 participants. The carrier screening results showed that 72.1% were heterozygous for at least 1 severe disease-causing variant in 1 of the genes analyzed. The most common genes with severe disease-causing variants were CFTR (16.8% of participants), MEFV (11.5%), WNT10A (6.7%), and GBA (6.7%). The allele frequencies were compared with those in the gnomAD; 85% of variant frequencies were statistically different from those found in gnomAD (P <.05). Finally, 6% of couples were at risk of having a child with a severe disorder. Conclusion: The heterozygote frequency of at least 1 severe disease-causing variant in the MJC was 72.1%. The use of carrier screening in the MJC and other understudied populations could help parents make more informed decisions. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Automated summary

This study aimed to determine the heterozygote frequency of disease-causing variants in the Mexican Jewish community (MJC). The results showed that 72.1% of participants carried at least one severe disease-causing variant in the analyzed genes. The most common genes with severe disease-causing variants were CFTR, MEFV, WNT10A, and GBA. Comparison with the Genome Aggregation Database (gnomAD) revealed statistically significant differences in variant frequencies. Additionally, 6% of couples were at risk of having a child with a severe disorder. The study highlights the importance of using carrier screening in the MJC and other understudied populations to facilitate informed decision-making for parents.