Lessons learned from expanded reproductive carrier screening in self-reported Ashkenazi, Sephardi, and Mizrahi Jewish patients

Mol Genet Genomic Med. 2020 Feb;8(2):e1053. doi: 10.1002/mgg3.1053. Epub 2019 Dec 27.


Background: Next-generation sequencing (NGS)-based panels have gained traction as a strategy for reproductive carrier screening. Their value for screening Ashkenazi Jewish (AJ) individuals, who have benefited greatly from population-wide targeted testing, as well as Sephardi/Mizrahi Jewish (SMJ) individuals (an underserved population), has not been fully explored.

Methods: The clinical utilization by 6,805 self-reported Jewish individuals of an expanded NGS panel, along with several ancillary assays, was assessed retrospectively. Data were extracted for a subset of 96 diseases that, during the panel design phase, were classified as being AJ-, SMJ-, or pan-Jewish/pan-ethnic-relevant.

Results: 64.6% of individuals were identified as carriers of one or more of these 96 diseases. Over 80% of the reported variants would have been missed by following recommended AJ screening guidelines. 10.7% of variants reported for AJs were in "SMJ-relevant genes," and 31.2% reported for SMJs were in "AJ-relevant genes." Roughly 2.5% of individuals carried a novel, likely pathogenic variant. One in 16 linked cohort couples was identified as a carrier couple for at least one of these 96 diseases.

Conclusion: For maximal carrier identification, this study supports using expanded NGS panels for individuals of all Jewish backgrounds. This approach can better empower at-risk couples for reproductive decision making.

Keywords: Ashkenazi Jewish; Sephardi/Mizrahi Jewish; carrier couple; expanded carrier screening; preconception/prenatal genetic testing.

MeSH terms

  • Genetic Carrier Screening / standards
  • Genetic Carrier Screening / statistics & numerical data*
  • Genetic Diseases, Inborn / ethnology*
  • Genetic Diseases, Inborn / genetics
  • High-Throughput Nucleotide Sequencing / standards
  • High-Throughput Nucleotide Sequencing / statistics & numerical data
  • Humans
  • Jews / genetics*
  • Practice Guidelines as Topic
  • Preconception Care / standards
  • Preconception Care / statistics & numerical data