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Original research
Expanded targeted preconception screening panel in Israel: findings and insights
  1. Adi Reches1,2,
  2. Vered Ofen Glassner1,
  3. Nurit Goldstein3,
  4. Josepha Yeshaya4,
  5. Galit Delmar5,
  6. Ellie Portugali5,
  7. Tova Hallas5,
  8. Amit Weinstein1,
  9. Alina Kurolap1,
  10. Michal Berkenstadt3,6,
  11. Tal Mantsour4,
  12. Liat Abu-Gutstein3,
  13. Liat Ries-Levavi3,
  14. Haike Reznik-Wolf3,6,
  15. Doron Moshe Behar5,
  16. Yuval Yaron1,6,
  17. Elon Pras3,6,
  18. Hagit Baris Feldman1,6
  1. 1The Genetics Institute and Genomics Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
  2. 2Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
  3. 3The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel
  4. 4American Medical Genetics (AMG) Laboratory, Herzliya, Israel
  5. 5Igentify, Caesarea, Israel
  6. 6Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
  1. Correspondence to Dr Hagit Baris Feldman, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel; hagitbf{at}tlvmc.gov.il

Abstract

Background We aimed to analyse the efficacy and added value of a targeted Israeli expanded carrier screening panel (IL-ECSP), beyond the first-tier test covered by the Israeli Ministry of Health (IMOH) and the second-tier covered by the Health Maintenance Organisations (HMOs).

Methods A curated variant-based IL-ECSP, tailored to the uniquely diverse Israeli population, was offered at two tertiary hospitals and a major genetics laboratory. The panel includes 1487 variants in 357 autosomal recessive and X-linked genes.

Results We analysed 10 115 Israeli samples during an 18-month period. Of these, 6036 (59.7%) were tested as couples and 4079 (40.3%) were singles. Carriers were most frequently identified with mutations in the following genes: GJB2/GJB6 (1:22 allele frequency), CFTR (1:28), GBA (1:34), TYR (1:39), PAH (1:50), SMN1 (1:52) and HEXA (1:56). Of 3018 couples tested, 753 (25%) had no findings, in 1464 (48.5%) only one partner was a carrier, and in 733 (24.3%) both were carriers of different diseases. We identified 79 (2.6%) at-risk couples, where both partners are carriers of the same autosomal recessive condition, or the female carries an X-linked disease. Importantly, 48.1% of these would not have been detected by ethnically-based screening tests currently provided by the IMOH and HMOs, for example, variants in GBA, TYR, PAH and GJB2/GJB6.

Conclusion This is the largest cohort of targeted ECSP testing, tailored to the diverse Israeli population. The IL-ECSP expands the identification of couples at risk and empowers their reproductive choices. We recommend endorsing an expanded targeted panel to the National Genetic Carrier Screening programme.

  • Inborn Genetic Diseases
  • Genetic Carrier Screening
  • Genetic Counseling

Data availability statement

Data are available upon reasonable request. Data related to study results is available upon reasonable request.

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Data availability statement

Data are available upon reasonable request. Data related to study results is available upon reasonable request.

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Footnotes

  • AR, VOG and NG contributed equally.

  • YY, EP and HBF contributed equally.

  • Contributors Study conceptions and design: DMB and HBF. Data acquirement: AR, VOG, NG, JY, GD, EPo, TH, AW, MB, TM, LA-G, LR-L and HR-W. Results interpretation: AR, VOG, GD, EPo, TH, AK, YY, EPr and HBF. Manuscript drafting and revision: AR, VOG, AK and HBF drafted the manuscript. Guarantor: HBF. All authors reviewed and revised the manuscript, and approved the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests DMB was involved in the design of the CarrierScan array and is entitled to certain royalties.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.