Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain)

• Published in: Clinical genetics Vol. 106; no. 4; pp. 525 - 531
• Main Authors: Pitiot, Ana S., Blay, Pilar, Díaz‐Navarro, Ander, Fernández‐Arrojo, Sara, Romero, Rosa, Álvarez‐Eguiluz, Ángel, Alvarado, Marta G., Álvarez, Nieves, García‐Teijido, Paula, Fernández, Yolanda, Palacio, Isabel, Puente, Xose S., Balbín, Milagros
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2024
• Subjects: Adult; BRCA; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Exons - genetics; Female; founder; Genetic Predisposition to Disease; Germ-Line Mutation - genetics; haplotype study; Haplotypes; Haplotypes - genetics; Humans; Male; Middle Aged; Nucleotides; Pathogenicity; Pedigree; Spain - epidemiology; splicing analysis; variant age; Spain; BRCA; splicing analysis; variant age; haplotype study; founder
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.14580

The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470_471del and c.3331_3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901_2902dup) and two in BRCA2 (c.2095C>T and c.4040_4035delinsC). A common haplotype was established for all recurrent variants indicating a shared ancestral origin. Three splicing analyses are shown: BRCA1:c.5152+3A>C and BRCA1:c.5333‐3T>G that lead to skipping of exon 18, and 22 respectively, and BRCA1:c.5278‐1G>T giving rise to two transcripts, one lacking exon 21 (p.Ille1760Glyfs*60) and one lacking the first 8 nucleotides of exon 21 (p.Phe1761Asnfs*14), supporting pathogenicity for these variants. BRCA1/2 mutational landscape of Asturias reveals that seven recurrent variants are present in >50% carriers. Four of these variants are founder from this region at the North of Spain.