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

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

doi:10.1186/s12881-019-0814-y

Abstract

BackgroundPathogenic 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.MethodsAn 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.ResultsWe 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.ConclusionsThis 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.

Highlights

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
The variant was likely transmitted to the index case by her mother (III-2) even though she was not diagnosed with breast cancer, but has a sister who died of breast cancer
For the other 14 index cases recruited for BRCA1/ BRCA2 genetic testing, we identified a recurrent pathogenic variant of the BRCA1 gene in 6 families out of the 14

Summary

Introduction

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. Genetic variation analysis of BRCA2 has identified a large number of different pathogenic germline variants in breast cancer patients and more than a thousand different disease–causing germline pathogenic variants were listed in the Breast Cancer Information Core Database (BIC; http://research.nhgri.nih.gov/ bic/) and in the ClinVar database Most BRCA2 pathogenic variants have been reported in individuals of European and Asian origin while limited information is available on SSA populations [15,16,17,18,19]. We report a novel pathogenic variant in BRCA2 in a consanguineous family with a family history of breast cancer

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Results

Discussion

Conclusion