{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:02:21Z","timestamp":1791129741620,"version":"4.1.0"},"reference-count":12,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Few germline <jats:italic>BRCA2<\/jats:italic> rearrangements have been described compared with the large number of germline rearrangements reported in the <jats:italic>BRCA1<\/jats:italic> gene. However, some <jats:italic>BRCA2<\/jats:italic> rearrangements have been reported in families that included at least one case of male breast cancer.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Objective:<\/jats:bold> To estimate the contribution of large genomic rearrangements to the spectrum of <jats:italic>BRCA2<\/jats:italic> defects.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> Quantitative multiplex PCR of short fluorescent fragments (QMPSF) was used to screen the <jats:italic>BRCA2<\/jats:italic> gene for germline rearrangements in highly selected families. QMPSF was previously used to detect heterozygous deletions\/duplications in many genes including <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic>.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> We selected a subgroup of 194 high risk families with four or more breast cancers with an average age at diagnosis of \u2a7d50 years, who were recruited through 14 genetic counselling centres in France and one centre in Switzerland. <jats:italic>BRCA2<\/jats:italic> mutations were detected in 18.6% (36 index cases) and <jats:italic>BRCA1<\/jats:italic> mutations in 12.4% (24 index cases) of these families. Of the 134 <jats:italic>BRCA1\/2<\/jats:italic> negative index cases in this subgroup, 120 were screened for large rearrangements of <jats:italic>BRCA2<\/jats:italic> using QMPSF. Novel and distinct <jats:italic>BRCA2<\/jats:italic> deletions were detected in three families and their boundaries were determined. We found that genomic rearrangements represent 7.7% (95% confidence interval 0% to 16%) of the <jats:italic>BRCA2<\/jats:italic> mutation spectrum.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion:<\/jats:bold> The molecular diagnosis of breast cancer predisposition should include screening for <jats:italic>BRCA2<\/jats:italic> rearrangements, at least in families with a high probability of <jats:italic>BRCA2<\/jats:italic> defects.<\/jats:p>","DOI":"10.1136\/jmg.2005.040212","type":"journal-article","created":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T16:31:57Z","timestamp":1157128317000},"page":"e49-e49","source":"Crossref","is-referenced-by-count":53,"title":["The contribution of germline rearrangements to the spectrum of <i>BRCA2<\/i> 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