乳腺癌（BC）是利比亚妇女癌症死亡的主要原因。由于基因组成和人群历史的多样性，BRCA1 变体在全球范围内存在差异。它们在利比亚的分布、流行程度和重要性在很大程度上仍未得到探索。本研究调查了利比亚 BC 家族中外显子 5、11 和 20 中 BRCA1 变异的特征和分布。 2018-2020年从33个无关家庭中选取36例年龄≤45岁、46-50岁、近亲有乳腺癌、卵巢癌、胰腺癌或前列腺癌家族史或三阴性BC患者在利比亚萨布拉塔国家癌症研究所。使用 Sanger 测序对这 33 个家庭中的 20 名女性（18 名 BC 患者和两名未受影响的患者）进行了 BRCA1 外显子 5、11 和 20 筛查。所有家庭都完成了流行病学和家族史调查问卷。在18个无关家族中的10个（55.6%）中检测到27个变异（外显子11中有26个，外显子20中有1个，次要等位基因频率 < 0.01）。在27个变异中，26个（96%）是杂合的。鉴定出一种移码致病变异 c.2643del 和一种新变异 c.1366A>G。此外，还检测到了 7 个临床意义未知的变异：c.1158T>A、c.1346C>G、c.1174C>G、c.3630 G>T、c.3599A>T 和 c.3400 G>C。外显子 11 中，c.5244T>A 位于外显子 20 中。具有相互冲突的致病性解释的六种变体，c． 3460T>A，c。第3572章3700 G>C，c。 1246C>G，c。 1344C>G，并且c．还鉴定出1054 G>A。鉴定出十二种良性/可能良性变异。在利比亚患者中发现了北非未报告的罕见 BRCA1 变异。这些发现为可能导致利比亚人遗传性 BC 风险的 BRCA1 变异提供了初步见解。进一步的功能、计算和群体分析对于确定它们对 BC 风险的重要性和潜在影响至关重要，这最终可能导致更加个性化的管理策略。

Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. BRCA1 variants differ globally due to the diversity of genetic makeup and populations history. Their distribution, prevalence, and significance in Libyans remain largely unexplored. This study investigated the characteristics and distribution of BRCA1 variants in exons 5, 11, and 20 in Libyan families with BC. Thirty-six BC patients at ≤ 45 years, between 46-50 years and with a family history of breast, ovarian, pancreatic or prostate cancer in close relatives, or with triple-negative BC, were selected from 33 unrelated families during 2018-2020 at the National Cancer Institute, Sabratha, Libya. From these 33 families, 20 women (18 BC patients and two unaffected) were screened for BRCA1 exons 5, 11 and 20 using Sanger sequencing. All families completed an epidemiology and family history questionnaire. Twenty-seven variants (26 in exon 11 and 1 in exon 20, minor allele frequency of < 0.01) were detected in 10 of 18 unrelated families (55.6%.) Among the 27 variants, 26 (96%) were heterozygous. A frameshift pathogenic variant, c.2643del, and one novel variant c.1366A>G were identified. Furthermore, seven variants with unknown clinical significance were detected: c.1158T>A, c.1346C>G, c.1174C>G, c.3630 G>T, c.3599A>T, and c.3400 G>C in exon 11, and c.5244T>A in exon 20. Six variants with conflicting pathogenicity interpretations, c. 3460T>A, c. 3572 G>A, c. 3700 G>C, c. 1246C>G, c. 1344C>G, and c. 1054 G>A, were also identified. Twelve benign/likely benign variants were identified. Rare BRCA1 variants that have not been reported in North Africa were found in Libyan patients. These findings provide preliminary insights into the BRCA1 variants that could contribute to hereditary BC risk in Libyans. Further functional, computational, and population analyses are essential to determine their significance and potential impact on BC risk, which could ultimately lead to more personalized management strategies.