{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T01:03:24Z","timestamp":1772931804253,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2004,9,7]],"date-time":"2004-09-07T00:00:00Z","timestamp":1094515200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Germline mutations in <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> predispose to breast and ovarian cancer. A multitude of mutations have been described and are found to be scattered throughout these two large genes. We describe analysis of <jats:italic>BRCA1<\/jats:italic> in 25 individuals from 18 families from a Greek cohort.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>The approach used is based on dHPLC mutation screening of the <jats:italic>BRCA1<\/jats:italic> gene, followed by sequencing of fragments suspected to carry a mutation including intron \u2013 exon boundaries. In patients with a strong family history but for whom no mutations were detected, analysis was extended to exons 10 and 11 of the <jats:italic>BRCA2<\/jats:italic> gene, followed by MLPA analysis for screening for large genomic rearrangements.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>A pathogenic mutation in <jats:italic>BRCA1<\/jats:italic> was identified in 5\/18 (27.7 %) families, where four distinct mutations have been observed. Single base putative pathogenic mutations were identified by dHPLC and confirmed by sequence analysis in 4 families: 5382insC (in two families), G1738R, and 5586G &gt; A (in one family each). In addition, 18 unclassified variants and silent polymorphisms were detected including a novel silent polymorphism in exon 11 of the <jats:italic>BRCA1<\/jats:italic> gene. Finally, MLPA revealed deletion of exon 20 of the <jats:italic>BRCA1<\/jats:italic> gene in one family, a deletion that encompasses 3.2 kb of the gene starting 21 bases into exon 20 and extending 3.2 kb into intron 20 and leads to skipping of the entire exon 20. The 3' breakpoint lies within an <jats:italic>Alu<\/jats:italic>Sp repeat but there are no recognizable repeat motifs at the 5' breakpoint implicating a mechanism different to <jats:italic>Alu<\/jats:italic>-mediated recombination, responsible for the majority of rearrangements in the <jats:italic>BRCA1<\/jats:italic> gene.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>We conclude that a combination of techniques capable of detecting both single base mutations and small insertions \/ deletions and large genomic rearrangements is necessary in order to accurately analyze the <jats:italic>BRCA1<\/jats:italic> gene in patients at high risk of carrying a germline mutation as determined by their family history. Furthermore, our results suggest that in those families with strong evidence of linkage to the <jats:italic>BRCA1<\/jats:italic> locus in whom no point mutation has been identified re-examination should be carried out searching specifically for genomic rearrangements.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2407-4-61","type":"journal-article","created":{"date-parts":[[2004,9,14]],"date-time":"2004-09-14T06:23:39Z","timestamp":1095143019000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Characterization of a novel large deletion and single point mutations in the BRCA1gene in a Greek cohort of families with suspected hereditary breast cancer"],"prefix":"10.1186","volume":"4","author":[{"given":"Ioulia","family":"Belogianni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Apessos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markos","family":"Mihalatos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangelia","family":"Razi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanos","family":"Labropoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Petounis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki","family":"Gaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios","family":"Keramopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikos","family":"Pandis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyriacos","family":"Kyriacou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Hadjisavvas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paris","family":"Kosmidis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drakoulis","family":"Yannoukakos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Nasioulas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2004,9,7]]},"reference":[{"key":"151_CR1","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/87876","volume":"7","author":"KN Nathanson","year":"2001","unstructured":"Nathanson KN, Wooster R, Webber BL: Breast cancer genetics: What we know and what we need. 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