{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:12:15Z","timestamp":1791335535997,"version":"4.3.1"},"reference-count":37,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p>\n                  <jats:bold>Purpose:<\/jats:bold> To develop a simple scoring system for the likelihood of identifying a <jats:italic>BRCA1<\/jats:italic> or <jats:italic>BRCA2<\/jats:italic> mutation.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> DNA samples from affected subjects from 422 non-Jewish families with a history of breast and\/or ovarian cancer were screened for <jats:italic>BRCA1<\/jats:italic> mutations and a subset of 318 was screened for <jats:italic>BRCA2<\/jats:italic> by whole gene screening techniques. Using a combination of results from screening and the family history of mutation negative and positive kindreds, a simple scoring system (Manchester scoring system) was devised to predict pathogenic mutations and particularly to discriminate at the 10% likelihood level. A second separate dataset of 192 samples was subsequently used to test the model\u2019s predictive value. This was further validated on a third set of 258 samples and compared against existing models.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> The scoring system includes a cut-off at 10 points for each gene. This equates to &gt;10% probability of a pathogenic mutation in <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> individually. The Manchester scoring system had the best trade-off between sensitivity and specificity at 10% prediction for the presence of mutations as shown by its highest C-statistic and was far superior to BRCAPRO.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion:<\/jats:bold> The scoring system is useful in identifying mutations particularly in <jats:italic>BRCA2<\/jats:italic>. The algorithm may need modifying to include pathological data when calculating whether to screen for <jats:italic>BRCA1<\/jats:italic> mutations. It is considerably less time-consuming for clinicians than using computer models and if implemented routinely in clinical practice will aid in selecting families most suitable for DNA sampling for diagnostic testing.<\/jats:p>","DOI":"10.1136\/jmg.2003.017996","type":"journal-article","created":{"date-parts":[[2004,6,1]],"date-time":"2004-06-01T12:53:10Z","timestamp":1086094390000},"page":"474-480","source":"Crossref","is-referenced-by-count":244,"title":["A new scoring system for the chances of identifying a <i>BRCA1\/2<\/i> mutation outperforms existing models including BRCAPRO"],"prefix":"10.1136","volume":"41","author":[{"given":"D G R","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D M","family":"Eccles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Bulman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Amir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Shenton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Lalloo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2004,6,1]]},"reference":[{"key":"2025101714080315000_41.6.474.1","doi-asserted-by":"publisher","DOI":"10.1086\/301749"},{"key":"2025101714080315000_41.6.474.2","doi-asserted-by":"publisher","DOI":"10.1086\/301614"},{"key":"2025101714080315000_41.6.474.3","first-page":"1013","volume":"60","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2025101714080315000_41.6.474.4","first-page":"3663","volume":"56","year":"1996","journal-title":"Cancer Res"},{"key":"2025101714080315000_41.6.474.5","first-page":"207","volume":"77","year":"2000","journal-title":"Am J Hum Genet"},{"key":"2025101714080315000_41.6.474.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.12.e42"},{"key":"2025101714080315000_41.6.474.7","doi-asserted-by":"publisher","DOI":"10.1086\/301670"},{"key":"2025101714080315000_41.6.474.8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705153362002"},{"key":"2025101714080315000_41.6.474.9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550150046034"},{"key":"2025101714080315000_41.6.474.10","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1200\/JCO.1998.16.7.2417","volume":"16","year":"1998","journal-title":"J Clin Oncol"},{"key":"2025101714080315000_41.6.474.11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.6.1480"},{"key":"2025101714080315000_41.6.474.12","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10223"},{"key":"2025101714080315000_41.6.474.13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.05.121"},{"key":"2025101714080315000_41.6.474.14","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.11.844"},{"key":"2025101714080315000_41.6.474.15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.07.007"},{"key":"2025101714080315000_41.6.474.16","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.7.503"},{"key":"2025101714080315000_41.6.474.17","unstructured":"Peelen T. Genetics of hereditary breast and ovarian cancer in the Netherlands. Leiden, The Netherlands: PhD thesis, Leiden University, 2001:115\u201328."},{"key":"2025101714080315000_41.6.474.18","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1626"},{"key":"2025101714080315000_41.6.474.19","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10527"},{"key":"2025101714080315000_41.6.474.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12856-5"},{"key":"2025101714080315000_41.6.474.21","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.10.792"},{"key":"2025101714080315000_41.6.474.22","first-page":"131","volume":"3","year":"2002","journal-title":"Familial Cancer"},{"key":"2025101714080315000_41.6.474.23","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1038\/bjc.1998.366","volume":"77","year":"1998","journal-title":"Br J Cancer"},{"key":"2025101714080315000_41.6.474.24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10325"},{"key":"2025101714080315000_41.6.474.25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.09.023"},{"key":"2025101714080315000_41.6.474.26","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.1.10"},{"key":"2025101714080315000_41.6.474.27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705153362003"},{"key":"2025101714080315000_41.6.474.28","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.11.943"},{"key":"2025101714080315000_41.6.474.29","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.16.1215"},{"key":"2025101714080315000_41.6.474.30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199601183340301"},{"key":"2025101714080315000_41.6.474.31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/bcr410","volume":"4","year":"2001","journal-title":"Breast Cancer Res"},{"key":"2025101714080315000_41.6.474.32","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.9.e107"},{"key":"2025101714080315000_41.6.474.33","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1200\/JCO.1996.14.5.1730","volume":"14","year":"1996","journal-title":"J Clin Oncol"},{"key":"2025101714080315000_41.6.474.34","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(00)80014-3"},{"key":"2025101714080315000_41.6.474.35","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.15.1310"},{"key":"2025101714080315000_41.6.474.36","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2000.580408.x"},{"key":"2025101714080315000_41.6.474.37","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600008"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2003.017996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T21:08:12Z","timestamp":1760735292000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2003.017996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2004,6,1]]},"published-print":{"date-parts":[[2004,6]]}},"alternative-id":["10.1136\/jmg.2003.017996"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2003.017996","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,6]]}}}