Double Heterozygosity for Rare Deleterious Variants in the BRCA1 and BRCA2 Genes in a Hungarian Patient with Breast Cancer

Hereditary breast cancer is most commonly attributed to germline BRCA1 and BRCA2 gene variants. The vast majority of BRCA1 and BRCA2 mutation carriers are single heterozygotes, and double heterozygosity (DH) is a very rare finding. Here, we describe the case of a BRCA1/BRCA2 double heterozygous female proband diagnosed with breast cancer. Genetic testing for hereditary breast and ovarian cancer revealed two pathogenic variants in the BRCA1 (c.5095C>T, p.(Arg1699Trp)) and in BRCA2 genes (c.658_659delGT, p.(Val220Ilefs*4)) in heterozygous form. None of the variants were founder Jewish mutations; to our knowledge, these rare deleterious variants have not been previously described in DH patients in the literature. The patient had triple-negative unilateral breast cancer at the age of 36 and 44 years. Based on family studies, the BRCA1 variant was maternally inherited.

Automated summary

Here, we present a case of a female patient carrying double heterozygous mutations in the BRCA1 and BRCA2 genes, who was diagnosed with breast cancer. Genetic testing revealed two pathogenic variants in the BRCA1 gene (c.5095C>T, p.(Arg1699Trp)) and one pathogenic variant in the BRCA2 gene (c.658_659delGT, p.(Val220Ilefs*4)). These rare deleterious mutations are not commonly found in the Jewish population and have not been previously reported in double heterozygous patients.