A common pathogenic founder variant in Rwandan breast cancer cases.

Authors

Achille V C Manirakiza, Shakuntala Baichoo, Annette Uwineza, Damas Dukundane, Eulade Rugengamanzi, Janviere Mutamuliza, Allison M O Niragira, Raissa Muvunyi, Jeffrey Besada, Sarah M Nielsen, Brianna Bucknor, Diane R Koeller, Caroline Andrews, Leon Mutesa, Temidayo Fadelu, Timothy R Rebbeck

Published in

PLoS genetics. Volume 22. Issue 11. Pages e1012180. Nov 02, 2026. Epub Nov 02, 2026.

Abstract

Germline data from African populations remain sparse, limiting characterization of population-specific BRCA1/2 pathogenic variants (PV). In a study of 175 Rwandan women with breast cancer, 7 unrelated carriers (4% of cases; 22% of PV carriers) harbored the same BRCA1 frameshift PVs, c.4065_4068del (p.Asn1355Lysfs*10), which is extremely rare in gnomAD yet recurrent in European, Asian, and Middle Eastern cohorts. Whole-exome sequencing and haplotype analysis of all 7 carriers revealed a shared ancestral block of approximately 581 kb surrounding the variant, and extended haplotype homozygosity and network analyses confirmed a common founder origin. Coalescent-based age estimation placed the founder event approximately 4,000--10,000 years ago. Comparison with 1000 Genomes Project data showed the founder haplotype is absent or exceedingly rare outside African and South Asian populations. These findings strongly suggest the c.4065_4068del variant as a pre-historical BRCA1 founder variant in Rwanda, with implications for targeted genetic testing, cascade screening, and cancer prevention in the region.

PMID:
42970609
Bibliographic data and abstract were imported from PubMed on 03 Nov 2026.

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