Germline pathogenic variants (PVs) in BRCA1/BRCA2 are well-established risk factors for breast cancer (BC) and/or ovarian cancer (OC). Founder PVs have been described in BRCA1/ BRCA2 in several genetic isolates. The Christian Arab population in the Middle East is a relatively isolated ethnic group, yet founder, or recurrent BRCA1/BRCA2 PVs have not been reported in this population. In this study we describe PVs detected in cancer susceptibility genes among a cohort of Christian Arabs from Israel. We reviewed patient records from the Oncogenetic clinic at Rambam Health Care Campus during the years 2013- mid 2020. Thirty-five unrelated Christian Arab patients, with personal or family history of BC and/or OC underwent BRCA1/BRCA2 (14/35) testing or cancer gene panel testing (21/35) as part of their diagnostic workup. Three clinically significant variants in BRCA2, CHEK2 and RAD51C were found in 7/35 patients (20%). A recurrent duplication of the BRCA2 genomic region, encompassing exons 5–10 and the 5' portion of exon 11, was found in 5/33 (15.2%) patients for whom copy number variants (CNVs) analysis was performed. We identified a recurrent pathogenic BRCA2 duplication in Christian Arab patients with a personal/ family history of BC and/or OC. Our findings emphasize the importance of inclusion of CNVs analysis in BRCA1/BRCA2 genetic testing, and specifically for Christian Arab patients suspected of hereditary BC and/or OC.

BRCA1/BRCA2中的生殖系致病变异 (PV)是乳腺癌 (BC) 和/或卵巢癌 (OC) 的公认危险因素。Founder PVs 已在几个遗传分离物中的BRCA1 / BRCA2中描述。中东的基督教阿拉伯人口是一个相对孤立的种族群体，但尚未在该人群中报告创始人或复发性BRCA1/BRCA2 PVs。在这项研究中，我们描述了在来自以色列的一群基督教阿拉伯人的癌症易感基因中检测到的 PV。我们回顾了 2013 年至 2020 年年中 Rambam 医疗保健园区肿瘤遗传学诊所的患者记录。 35 名具有 BC 和/或 OC 个人或家族史的无关基督教阿拉伯患者接受了治疗。BRCA1/BRCA2 (14/35) 检测或癌症基因组检测 (21/35) 作为诊断检查的一部分。在 7/35 的患者 (20%) 中发现了BRCA2、CHEK2和RAD51C的三个临床显着变异。BRCA2基因组区域的重复重复，包括外显子 5-10 和外显子 11 的 5' 部分，在 5/33 (15.2%) 进行拷贝数变异 (CNV) 分析的患者中发现。我们在有 BC 和/或 OC 的个人/家族史的基督教阿拉伯患者中发现了复发性致病性BRCA2重复。我们的研究结果强调了将 CNV 分析纳入BRCA1/BRCA2的重要性基因检测，特别是针对疑似遗传性 BC 和/或 OC 的基督教阿拉伯患者。