Expanded targeted preconception screening panel in Israel: findings and insights

• Published in: Journal of medical genetics p. jmg-2023-109629
• Main Authors: Reches, Adi, Ofen Glassner, Vered, Goldstein, Nurit, Yeshaya, Josepha, Delmar, Galit, Portugali, Ellie, Hallas, Tova, Weinstein, Amit, Kurolap, Alina, Berkenstadt, Michal, Mantsour, Tal, Abu-Gutstein, Liat, Ries-Levavi, Liat, Reznik-Wolf, Haike, Behar, Doron Moshe, Yaron, Yuval, Pras, Elon, Baris Feldman, Hagit
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.08.2024
• Subjects: Blood diseases; Cystic fibrosis; Decision making; Ethnicity; Gene frequency; Genes; Genetic screening; Genetics; Genomics; Health insurance; Jewish people; Mutation; Pediatrics; Self report; Tel Aviv Israel; Israel; Inborn Genetic Diseases; Genetic Counseling; Genetic Carrier Screening
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg-2023-109629

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). 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. 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: (1:22 allele frequency), (1:28), (1:34), (1:39), (1:50), (1:52) and (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 . 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.