TY - JOUR
T1 - Expanded targeted preconception screening panel in Israel
T2 - findings and insights
AU - Reches, Adi
AU - Ofen Glassner, Vered
AU - Goldstein, Nurit
AU - Yeshaya, Josepha
AU - Delmar, Galit
AU - Portugali, Ellie
AU - Hallas, Tova
AU - Weinstein, Amit
AU - Kurolap, Alina
AU - Berkenstadt, Michal
AU - Mantsour, Tal
AU - Abu-Gutstein, Liat
AU - Ries-Levavi, Liat
AU - Reznik-Wolf, Haike
AU - Behar, Doron Moshe
AU - Yaron, Yuval
AU - Pras, Elon
AU - Baris Feldman, Hagit
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2024/7/19
Y1 - 2024/7/19
N2 - 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.
AB - 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.
KW - Genetic Carrier Screening
KW - Genetic Counseling
KW - Inborn Genetic Diseases
UR - http://www.scopus.com/inward/record.url?scp=85193254054&partnerID=8YFLogxK
U2 - 10.1136/jmg-2023-109629
DO - 10.1136/jmg-2023-109629
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C2 - 38719349
AN - SCOPUS:85193254054
SN - 0022-2593
VL - 61
SP - 783
EP - 787
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 8
ER -