Double Heterozygous Mutations in the BRCA2 and ATM Genes: A Case Report and Review of the Literature

Abstract

<b><i>Introduction:</i></b> Germline mutations of the <i>BRCA1</i> and <i>BRCA2</i> genes are responsible for about a quarter of hereditary breast cancers (BCs). In this study, we aimed to determine the importance of rare double heterozygous (DH) pathogenic variant carriership in <i>BRCA2</i>and <i>ATM</i> genes in a patient diagnosed with BC and pancreas cancer (PC). <b><i>Case Report:</i></b> A 54-year-old female patient was diagnosed with BC at the age of 34 years and with PC at the age of 48 years. The multigene panel and next-generation sequencing technique were used to evaluate the status of the patient’s cancer susceptibility genes. Pathogenic variants c.537dup (p.Ile180Tyrfs*3) in the <i>BRCA2</i> gene and c.5065C&#x3e;T (p.Gln1689Ter) in the <i>ATM</i> gene were detected as DH in the patient. Co-segregation analysis was performed on the relatives of the patient using Sanger sequencing. <b><i>Discussion/Conclusion:</i></b> Multiple primary malignant neoplasms can be encountered more frequently in DH pathogenic variant carriers, and the diagnosis of malignancies can be made at an earlier age through surveillance guided by genetic testing. In this rare case, more patient studies are needed to determine the contribution of DH in <i>BRCA2</i> and <i>ATM</i> genes to the phenotype.