Expanded targeted preconception screening panel in Israel: findings and insights.

Area of Science:

• Genetics
• Reproductive Medicine
• Population Screening

Background:

• Current genetic carrier screening in Israel includes first-tier (Ministry of Health) and second-tier (HMOs) tests.
• There is a need to evaluate the efficacy and added value of expanded carrier screening panels.
• The Israeli population's unique diversity necessitates tailored screening approaches.

Purpose of the Study:

• To analyze the efficacy and added value of a targeted Israeli expanded carrier screening panel (IL-ECSP).
• To compare IL-ECSP findings with existing national screening programs.
• To assess the potential for integrating expanded panels into national genetic screening.

Main Methods:

• A curated variant-based IL-ECSP was developed, targeting 1487 variants in 357 autosomal recessive and X-linked genes.
• The panel was offered at two tertiary hospitals and a major genetics laboratory.
• 10,115 Israeli samples were analyzed over an 18-month period.

Main Results:

• Carrier status was identified for common genes including GJB2/GJB6 (1:22), CFTR (1:28), and GBA (1:34).
• Of 3018 couples tested, 24.3% had both partners as carriers of different conditions, and 2.6% were identified as at-risk couples.
• 48.1% of at-risk couples identified by IL-ECSP would not have been detected by current ethnically-based screening tests.

Conclusions:

• The IL-ECSP is the largest cohort study of targeted expanded carrier screening in the diverse Israeli population.
• IL-ECSP significantly expands the identification of couples at risk for genetic conditions, empowering reproductive decisions.
• Endorsement of an expanded targeted panel is recommended for the National Genetic Carrier Screening program.