BackgroundPrevious studies have suggested that the prevalence of BRCA1 and 2 mutations in the Lebanese population is low despite the observation that the median age of breast cancer diagnosis is significantly lower than European and North American populations. We aimed at reviewing the rates and patterns of BRCA1/2 mutations found in individuals referred to the medical genetics unit at the American University of Beirut. We also evaluated the performance of clinical prediction tools.MethodsWe retrospectively reviewed the cases of all individuals undergoing BRCA mutation testing from April 2011 to May 2016. To put our findings in to context, we conducted a literature review of the most recently published data from the region.ResultsTwo-hundred eighty one individuals were referred for testing. The prevalence of mutated BRCA1 or 2 genes were 6 and 1.4% respectively. Three mutations accounted for 54% of the pathogenic mutations found. The BRCA1 c.131G > T mutation was found among 5/17 (29%) unrelated subjects with BRCA1 mutation and is unique to the Lebanese and Palestinian populations. For patients tested between 2014 and 2016, all patients positive for mutations fit the NCCN guidelines for BRCA mutation screening. The Manchester Score failed to predict pathogenic mutations.ConclusionThe BRCA1 c.131G > T mutation can be considered a founder mutation in the Lebanese population detected among 5/17 (29%) of individuals diagnosed with a mutation in BRCA1 and among 7/269 families in this cohort. On review of recently published data regarding the landscape of BRCA mutations in the Middle East and North Africa, each region appears to have a unique spectrum of mutations.

中文翻译：

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高危黎巴嫩受试者的 BRCA 突变筛查和模式

背景先前的研究表明，尽管观察到乳腺癌诊断的中位年龄明显低于欧洲和北美人群，但黎巴嫩人群中 BRCA1 和 2 突变的流行率较低。我们的目的是审查在贝鲁特美国大学医学遗传学单位提到的个体中发现的 BRCA1/2 突变的发生率和模式。我们还评估了临床预测工具的性能。方法我们回顾了 2011 年 4 月至 2016 年 5 月所有接受 BRCA 突变检测的个体的病例。为了将我们的发现与上下文联系起来，我们对来自region.Results 281 个人被转介进行测试。突变 BRCA1 或 2 个基因的患病率分别为 6 和 1。分别为 4%。三个突变占发现的致病突变的54%。BRCA1 c.131G > T 突变在 5/17 (29%) 的 BRCA1 突变无关受试者中发现，并且是黎巴嫩和巴勒斯坦人群所独有的。对于 2014 年至 2016 年间测试的患者，所有突变阳性患者均符合 NCCN BRCA 突变筛查指南。曼彻斯特评分未能预测致病性突变。结论 BRCA1 c.131G > T 突变可被认为是黎巴嫩人群中的创始人突变，在 5/17 (29%) 被诊断为 BRCA1 突变的个体和 7/269 个家庭中检测到在这个队列中。回顾最近公布的有关中东和北非 BRCA 突变情况的数据，每个地区似乎都有独特的突变谱。三个突变占发现的致病突变的54%。BRCA1 c.131G > T 突变在 5/17 (29%) 的 BRCA1 突变无关受试者中发现，并且是黎巴嫩和巴勒斯坦人群所独有的。对于 2014 年至 2016 年间测试的患者，所有突变阳性患者均符合 NCCN BRCA 突变筛查指南。曼彻斯特评分未能预测致病性突变。结论 BRCA1 c.131G > T 突变可被认为是黎巴嫩人群中的创始人突变，在 5/17 (29%) 被诊断为 BRCA1 突变的个体和 7/269 个家庭中检测到在这个队列中。回顾最近公布的有关中东和北非 BRCA 突变情况的数据，每个地区似乎都有独特的突变谱。三个突变占发现的致病突变的54%。BRCA1 c.131G > T 突变在 5/17 (29%) 的 BRCA1 突变无关受试者中发现，并且是黎巴嫩和巴勒斯坦人群所独有的。对于 2014 年至 2016 年间测试的患者，所有突变阳性患者均符合 NCCN BRCA 突变筛查指南。曼彻斯特评分未能预测致病性突变。结论 BRCA1 c.131G > T 突变可被认为是黎巴嫩人群中的创始人突变，在 5/17 (29%) 被诊断为 BRCA1 突变的个体和 7/269 个家庭中检测到在这个队列中。回顾最近公布的有关中东和北非 BRCA 突变情况的数据，每个地区似乎都有独特的突变谱。