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

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

BMC Medical Genetics

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

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

BMC Medical Genetics201920:73

https://doi.org/10.1186/s12881-019-0814-y

©  The Author(s). 2019

• Received: 8 October 2018
• Accepted: 24 April 2019
• Published: 6 May 2019

Open Peer Review reports

Abstract

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.

Keywords

• Hereditary breast cancer
• Susceptibility
• BRCA2 gene