Davidov Bella, Levon Amit, Volkov Hadas, Orenstein Naama, Karo Racheli, Fatal Gazit Inbal, Magal Nurit, Basel-Salmon Lina, Golan Mashiach Michal
Raphael Recanati Genetics Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
Applied Genomics LTD, Ness Ziona, Israel.
Clin Genet. 2022 May;101(5-6):517-529. doi: 10.1111/cge.14131. Epub 2022 Mar 29.
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.
孕前携带者筛查能够识别有生育患常染色体隐性和X连锁疾病后代风险的夫妇。在当今这个多民族的世界里，基于自我报告血统的筛查存在局限性。在此，我们以以色列犹太人群体为模型，描述了一项基于变异的全面泛民族携带者筛查的结果。该队列包括1696名个体（848对夫妇），他们接受了“MyScreen”多基因检测板的检测。该检测板涵盖了385个基因中的1206个变异，这些变异在不同的犹太族群以及当地的阿拉伯、德鲁兹和贝都因人群体中是已知的。其中，143个基因中的205个变异是犹太人群的始祖变异。我们鉴定出859名（50.6%）个体为151个基因中至少一个变异的携带者。重要的是，当前以色列的筛查项目可能会遗漏569名（66.2%）携带者。总体而言，“MyScreen”检测板识别出1:40（2.5%）的携带者夫妇，而基于血统的筛查发现的比例为1:144（0.7%）。令人惊讶的是，90名个体（10.5%）是其报告血统“意外”变异的携带者，并且有16个变异此前在犹太患者中未被报告。我们的结果支持了基于变异的全面携带者筛查在检测具有许多始祖致病变异的多样化人群中的携带者和高危夫妇方面的优势。
