RESUMO
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.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Adulto , Genes BRCA2 , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hungria , Predisposição Genética para Doença , Linhagem , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Mutação em Linhagem GerminativaRESUMO
Between January 1 1983 and December 31 2000, 21 cases of association of haematologic malignancies between parents and their children, two cases of that in grandparents and their grandchildren, and five cases of appearances of haematologic malignancies in uncle or aunt and their nephew or niece were experienced by authors. The diseases manifested in the second (or in the third) generation in 25/28 cases appeared earlier than those in the first generation, and in 13/28 cases had a greater malignity. In the remaining 15 cases the malignity was identical in both generation. Instead of anticipation (greater severity and/or earlier onset) the term dual acceleration (earlier onset and greater malignity) is more exact and thus more proper determine epidemiologic observations of authors. Dual acceleration was proved by authors not only in identical but in different haematologic malignancies manifested both in first-degree and second-degree relatives.