Evidence for an ancient BRCA1 pathogenic variant in inherited breast cancer patients from Senegal
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:QH426-470 lcsh:Medicine Biology Brief Communication 03 medical and health sciences Exon Breast cancer 0302 clinical medicine Gene duplication Genetics medicine Genetic predisposition Family history skin and connective tissue diseases Cancer genetics Molecular Biology Allele frequency Genetics (clinical) Haplotype lcsh:R medicine.disease lcsh:Genetics 030104 developmental biology 030220 oncology & carcinogenesis Founder effect |
| Zdroj: | npj Genomic Medicine, Vol 5, Iss 1, Pp 1-6 (2020) NPJ Genomic Medicine |
| ISSN: | 2056-7944 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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