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Case Reports
. 2021 Apr;186(2):569-575.
doi: 10.1007/s10549-021-06095-w. Epub 2021 Jan 28.

Concurrent germline BRCA1, BRCA2, and CHEK2 pathogenic variants in hereditary breast cancer: a case series

Jasmine Sukumar  1 , Mahmoud Kassem  1 , Doreen Agnese  2 , Robert Pilarski  3 , Bhuvaneswari Ramaswamy  1 , Kevin Sweet  3 , Sagar Sardesai  4
Affiliations
Case Reports

Concurrent germline BRCA1, BRCA2, and CHEK2 pathogenic variants in hereditary breast cancer: a case series

Jasmine Sukumar et al. Breast Cancer Res Treat. 2021 Apr.

Abstract

Background: Concurrent germline (g) pathogenic variants related to hereditary breast cancer represent a rare occurrence. While double heterozygosity in gBRCA1 and gBRCA2 has been reported in the past, herein we describe the first case of three known concurrent pathogenic variants identified in a family with a strong history of breast cancer. Case presentation The proband is a 55-year-old female diagnosed with synchronous bilateral breast cancers. She underwent a multi-gene panel testing indicating the presence of 3 concurrent heterozygous germline deleterious variants in BRCA1 (c.181T > G), BRCA2 (c.4398_4402delACATT), and CHEK2 (1100delC). The patient's two daughters (34 and 29 years-old) were found to be transheterozygous for inherited pathogenic variants in BRCA1 (c.181T > G) and CHEK2 (1100delC) genes.

Conclusion: The cancer risk and phenotypic manifestations associated with transheterozygous or multiple concurrent deleterious germline variants in hereditary breast cancer requires further investigation. A personalized approach to counseling, screening, and risk reduction should be undertaken for these individuals.

Keywords: BRCA1; BRCA2; Breast cancer; CHEK2; DNAI1; Genetic; Germline; Variants.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Family pedigree
See this image and copyright information in PMC

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