title: BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan.
abstract: Premenopausal breast cancer (BC) is one of the most common cancers of women in rural Africa and part of the disease load may be related to hereditary predisposition, including mutations in the BRCA1 gene. However, the BRCA1 mutations associated with BC in Africa are scarcely characterized. We report here 33 BRCA1 point mutations, among which 2 novel missense variants, found in 59 Central Sudanese premenopausal BC patients. The high fractions of mutations with intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4 %, respectively) are in agreement with the high genetic diversity expected in an African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0 %) overtly deleterious. Notably, in silico studies predict that the novel C-terminal missense variant c.5090G>A (p.Cys1697Tyr) affects phosphopeptide recognition by the BRCA1 BRCT1 domain and may have a pathogenic impact. Genetic variation and frequency of unique or rare mutations of uncertain clinical relevance pose significant challenges to BRCA1 testing in Sudan, as it might happen in other low-resource rural African contexts.
authors.affiliation: Institute for Genetic and Biomedical Research, National Research Council, Via Fantoli 16/15, 20138, Milan, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Biunno
authors.forename: Gitana
authors.initials: G
authors.lastname: Aceto
authors.forename: Khalid Dafaallah
authors.initials: KD
authors.lastname: Awadelkarim
authors.forename: Annalisa
authors.initials: A
authors.lastname: Morgano
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elhaj
authors.forename: Elgaylani Abdalla
authors.initials: EA
authors.lastname: Eltayeb
authors.forename: Dafalla Omer
authors.initials: DO
authors.lastname: Abuidris
authors.forename: Nasr Eldin
authors.initials: NE
authors.lastname: Elwali
authors.forename: Chiara
authors.initials: C
authors.lastname: Spinelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: De Blasio
authors.forename: Ermanna
authors.initials: E
authors.lastname: Rovida
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017697:Premenopause; D020836:Protein Structure, Quaternary; D013397:Sudan; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein
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