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However, only 20\u201330% of HBOC cases present pathogenic variants in those genes, and other DNA repair genes have emerged as increasing the risk for HBOC. In Brazil, variants in\n                      <jats:italic>ATM, ATR, CHEK2, MLH1, MSH2, MSH6, POLQ, PTEN,<\/jats:italic>\n                      and\n                      <jats:italic>TP53<\/jats:italic>\n                      genes have been reported in up to 7.35% of the studied cases. Here we screened and characterized variants in 21 DNA repair genes in HBOC patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically analyzed 708 amplicons encompassing the coding and flanking regions of 21 genes related to DNA repair pathways (\n                      <jats:italic>ABRAXAS1<\/jats:italic>\n                      ,\n                      <jats:italic>ATM, ATR, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MRE11, MSH2, MSH6, NBN, PALB2, PMS2, PTEN, RAD50, RAD51, TP53<\/jats:italic>\n                      and\n                      <jats:italic>UIMC1<\/jats:italic>\n                      ). A total of 95 individuals with HBOC syndrome clinical suspicion in Southeast Brazil were sequenced, and 25 samples were evaluated for insertions\/deletions in\n                      <jats:italic>BRCA1<\/jats:italic>\n                      \/\n                      <jats:italic>BRCA2<\/jats:italic>\n                      genes. Identified variants were assessed in terms of population allele frequency and their functional effects were predicted through in silico algorithms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 80 variants in 19 genes. About 23.4% of the patients presented pathogenic variants in\n                      <jats:italic>BRCA1, BRCA2<\/jats:italic>\n                      and\n                      <jats:italic>TP53<\/jats:italic>\n                      , a frequency higher than that identified among previous studies in Brazil. We identified a novel variant in\n                      <jats:italic>ATR<\/jats:italic>\n                      , which was predicted as pathogenic by in silico tools. The association analysis revealed 13 missense variants in\n                      <jats:italic>ABRAXAS1, BARD1, BRCA2, CHEK2, CDH1, MLH1, PALB2,<\/jats:italic>\n                      and\n                      <jats:italic>PMS2<\/jats:italic>\n                      genes, as significantly associated with increased risk to HBOC, and the patients carrying those variants did not present large insertions or deletions in\n                      <jats:italic>BRCA1\/BRCA2<\/jats:italic>\n                      genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study embodies the third report of a multi-gene analysis in the Brazilian population, and addresses the first report of many germline variants associated with HBOC in Brazil. Although further functional analyses are necessary to better characterize the contribution of those variants to the phenotype, these findings would improve the risk estimation and clinical follow-up of patients with HBOC clinical suspicion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-019-0652-y","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T08:03:04Z","timestamp":1581321784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population"],"prefix":"10.1186","volume":"13","author":[{"given":"Simone","family":"da Costa e Silva Carvalho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia Moreno","family":"Cury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle Barbosa","family":"Brotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Ferreira","family":"de Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginaldo Cruz Alves","family":"Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena Alves","family":"Texeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Rodrigues","family":"Pla\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Aparecida","family":"Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila Chagas","family":"Peronni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia de C\u00e1ssia","family":"Ruy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greice Andreotti","family":"Molfetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio Cesar","family":"Moriguti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirce Maria","family":"Carraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edenir In\u00eaz","family":"Palmero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ashton-Prolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Evangelista","family":"de Faria Ferraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-2886","authenticated-orcid":false,"given":"Wilson Araujo","family":"Silva Jr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,10]]},"reference":[{"key":"652_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1093\/bmb\/ldu034","volume":"112","author":"M Al Bakir","year":"2014","unstructured":"Al Bakir M, Gabra H. 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