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The germline mutational landscape of BRCA1 and BRCA2 in Brazil

2018; Nature Portfolio; Volume: 8; Issue: 1 Linguagem: Inglês

10.1038/s41598-018-27315-2

2045-2322

Edenir Inêz Palmero, Dirce Maria Carraro, Bárbara Alemar, María Manuela Martins, Ândrea Ribeiro‐dos‐Santos, Kiyoko Abe‐Sandes, Henrique C.R. Galvão, Rui Manuel Reis, Cristiano de Pádua Souza, Natália Campacci, Maria Isabel Achatz, Rafael Canfield Brianese, Maria Nirvana Formiga, Fabiana Baroni Alves Makdissi, Fernando Regla Vargas, Anna Cláudia Evangelista dos Santos, Héctor N. Seuánez, Kelly Rose Lobo de Souza, Cristina Brinkmann Oliveira Netto, Patrícia Santos-Silva, Gustavo Stumpf da Silva, Rommel Mário Rodríguez Burbano, Sidney Santos, Paulo Pimentel de Assumpção, Izabel Maria Monteiro Bernardes, Taísa Manuela Bonfim Machado-Lopes, Thaís Ferreira Bomfim, Maria Betânia Pereira Toralles, Ivana Nascimento, Bernardo Garicochea, Sérgio D. Simon, Simone Noronha, Fernanda Teresa de Lima, Anisse Marques Chami, Camila Matzenbacher Bittar, José Bines, Osvaldo Alfonso Pinto Artigalás, Maria Del Pilar Esteves-Diz, Tirzah Braz Petta Lajus, Ana Carolina Leite Vieira Costa Gifoni, Rodrigo Santa Cruz Guindalini, Terezinha Sarquis Cintra, Ida Vanessa Döederlein Schwartz, Pricila Bernardi, Diego Miguel, Sonia Tereza dos Santos Nogueira, Josef Herzog, Jeffrey N. Weitzel, Patrícia Ashton‐Prolla,

Genomics and Rare Diseases

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.