Pathogenic variant-based preconception carrier screening in the Israeli Jewish population.
Jewish population
NGS
at-risk couples rate
carrier frequency
pathogenic variants
preconception expanded pan-ethnic screening
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
15
03
2022
received:
08
12
2021
accepted:
16
03
2022
pubmed:
23
3
2022
medline:
7
5
2022
entrez:
22
3
2022
Statut:
ppublish
Résumé
Preconception carrier screening allows identification of couples at risk to have offspring with autosomal recessive and X-linked disorders. In a current multiethnic world, screening based on self-reported ancestry has limitations. Here we describe the findings of a comprehensive pan-ethnic variant-based carrier screening, using the Israeli Jewish population as a model. The cohort included 1696 individuals (848 couples) tested with the 'MyScreen' multigene panel. The panel covers 1206 variants spanning 385 genes, known in different Jewish ethnicities and local Arab, Druze and Bedouin populations. Out of these, 205 variants in 143 genes are Jewish founder variants. We identified 859 (50.6%), carriers of at least one variant in 151 genes. Importantly, 569 (66.2%) of carriers could be missed by the current Israeli screening program. In total, 1:40 (2.5%) of carrier couples were identified by the 'MyScreen' panel, compared with 1:144 (0.7%) found by the ethnicity-based screening. Surprisingly, 90 individuals (10.5%) were carriers of variants "unexpected" for their reported origin, and 16 variants were previously unreported in Jewish patients. Our results support the advantages of variant-based comprehensive carrier screening for detection of carriers and at-risk couples in a diverse population with many founder disease-causing variants.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
517-529Informations de copyright
© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.
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