Journal Article

Novel BRCA2 pathogenic variant c.5219 T > G; p.(Leu1740Ter) in a consanguineous Senegalese family with hereditary breast cancer

Dia, Yacouba, Ka, Sidy, Thiam, Alassane, Mbengue, Babacar, Diop, Jean Pascal Demba, Dieng, Mamadou Moustapha, Bourdon-Huguenin, Violaine, Ba, Seydi Abdoul, Diallo, Rokhaya Ndiaye, Diouf, Doudou, Dieye, Alioune, Sobol, Hagay, Faye, Oumar, Dem, Ahmadou, Diop, Papa Amadou

2019

Overview

Background Pathogenic variants associated with hereditary breast cancer have been reported for BRCA1 and BRCA2 (BRCA1/2) genes in patients from multiple ethnicities, but limited information is available from sub-Saharan African populations. We report a BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. Methods An index case from a consanguineous family and nineteen healthy female relatives were recruited after informed consent. Along with this family, 14 other index cases with family history of breast cancer were also recruited. For the control populations we recruited 48 healthy women with no cancer diagnosis and 48 women diagnosed with sporadic breast cancer without family history. Genomic DNA was extracted from peripheral blood. All BRCA2 exons were amplified by PCR and sequenced. Sequences were compared to the BRCA2 GenBank reference sequence (NM_000059.3) using Alamut Software. Results We identified a novel nonsense pathogenic variant c.5219 T > G; p.(Leu1740Ter) in exon 11 of BRCA2 in the index case. The pathogenic variant was also identified in three sisters and one daughter, but was absent in the controls and unrelated cases. Conclusions This is the first report of a novel BRCA2 pathogenic variant in a Senegalese family with hereditary breast cancer. This result confirms the diversity of hereditary breast cancer pathogenic variants across populations and extends our knowledge of genetic susceptibility to breast cancer in Africa.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adult / Aged / Aged, 80 and over / Analysis / Biomedical and Life Sciences / Biomedicine / BRCA mutations / BRCA1 protein / BRCA2 gene / BRCA2 protein / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cancer diagnosis / Clinical-Molecular Genetics and Cytogenetics / Consanguinity / Cytogenetics / Diagnosis / Disease susceptibility / EDTA / Exons / Family / Family medical history / Female / Gene Function / Genes / Genes, BRCA2 / Genetic aspects / Genetic Predisposition to Disease / Genetic susceptibility / Germ-Line Mutation / Health aspects / Health risk assessment / Hereditary breast cancer / Human Genetics / Humans / Identification and classification / Informed consent / Middle Aged / Mutation / Novels / Ovarian cancer / Peripheral blood / Research Article / Senegal / Survival Analysis / Susceptibility / Women's health