University Hospital, Mendoza, Argentina; Medical School, National University of Cuyo, Mendoza, Argentina.
Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, National Research Council of Argentine-National University of Cuyo, Mendoza, Argentina; Medical School, University of Mendoza, Mendoza, Argentina.
Cancer Genet. 2022 Jan;260-261:14-17. doi: 10.1016/j.cancergen.2021.11.003. Epub 2021 Nov 10.
Double heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. The proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants NM_007300.4(BRCA1):c.4201C>T (p.Gln1401Ter), and NM_000059.3(BRCA2):c.5146_5149del (p.Tyr1716fs). . The patient's son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. There are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.
BRCA1 和 BRCA2 基因中的双杂合致病性变异非常罕见，特别是在非阿什肯纳兹人群中。我们描述了首例非阿什肯纳兹裔阿根廷女性双侧乳腺癌的双杂合变异病例。该先证者为 65 岁女性，45 岁时被诊断为左乳浸润性导管癌，65 岁时被诊断为右乳浸润性癌。她进行了多基因panel 检测，结果显示存在两种同时存在的杂合性种系有害变异：NM_007300.4(BRCA1):c.4201C>T(p.Gln1401Ter)和 NM_000059.3(BRCA2):c.5146_5149del(p.Tyr1716fs)。患者的儿子（40 岁）被发现携带 BRCA2 基因的遗传致病性变异。在拉丁美洲，BRCA1 和 BRCA2 基因中的双杂合变异报告较少。我们患者中鉴定的两种致病性变异尚未被同时描述。
