Back to Search Start Over

Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal

Authors :
Alioune Dieye
Seydi Abdoul Ba
Doudou Diouf
Philomène Lopez Sall
Hagay Sobol
Serigne Modou Kane Gueye
Violaine Bourdon-Huguenin
Mamadou Moustapha Dieng
Ahmadou Dem
Babacar Mbengue
Sidy Ka
Oumar Faye
Aynina Cisse
Pape Saloum Diop
Papa Madieye Gueye
Jean Pascal Demba Diop
Maguette Sylla Niang
Ndiaye R
Yacouba Dia
Thiam A
Papa Amadou Diop
Source :
npj Genomic Medicine, Vol 5, Iss 1, Pp 1-6 (2020), NPJ Genomic Medicine
Publication Year :
2020
Publisher :
Nature Publishing Group, 2020.

Abstract

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p.Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing ~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred ~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.

Details

Language :
English
ISSN :
20567944
Volume :
5
Issue :
1
Database :
OpenAIRE
Journal :
npj Genomic Medicine
Accession number :
edsair.doi.dedup.....293fe5a384f6cbceb1393ccd0b9f0671