{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:38:11Z","timestamp":1791081491401,"version":"4.1.0"},"reference-count":13,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Autosomal dominant early onset Alzheimer\u2019s disease (ADEOAD) is genetically heterogeneous. Mutations of the <jats:italic>amyloid precursor protein (APP)<\/jats:italic>, <jats:italic>presenilin 1 (PSEN1)<\/jats:italic>, and <jats:italic>presenilin 2 (PSEN2)<\/jats:italic> genes have been identified.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Objective:<\/jats:bold> To further clarify the respective contribution of these genes to ADEOAD.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold> 31 novel families were investigated. They were ascertained using stringent criteria (the occurrence of probable or definite cases of Alzheimer\u2019s disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer\u2019s disease. The entire coding regions of <jats:italic>PSEN1<\/jats:italic> and <jats:italic>PSEN2<\/jats:italic> genes and exons 16 and 17 of <jats:italic>APP<\/jats:italic> gene were sequenced from genomic DNA<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold>\n                  <jats:italic>PSEN1<\/jats:italic> mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and <jats:italic>APP<\/jats:italic> mutations were found in five families. In this sample, the mean ages of disease onset in <jats:italic>PSEN1<\/jats:italic> and <jats:italic>APP<\/jats:italic> mutation carriers were 41.7 and 51.2 years, respectively.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to <jats:italic>PSEN1<\/jats:italic> mutations and 16% to <jats:italic>APP<\/jats:italic> mutations, while 18% remained unexplained.<\/jats:p>","DOI":"10.1136\/jmg.2005.033456","type":"journal-article","created":{"date-parts":[[2005,7,20]],"date-time":"2005-07-20T20:33:54Z","timestamp":1121891634000},"page":"793-795","source":"Crossref","is-referenced-by-count":160,"title":["Molecular diagnosis of autosomal dominant early onset Alzheimer\u2019s disease: an update: \n            Table 1"],"prefix":"10.1136","volume":"42","author":[{"given":"G","family":"Raux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Guyant-Mar\u00e9chal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Penet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Brice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Hannequin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Frebourg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Campion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2005,7,20]]},"reference":[{"key":"2025101713042098000_42.10.793.1","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"2025101713042098000_42.10.793.2","doi-asserted-by":"publisher","DOI":"10.1086\/302553"},{"key":"2025101713042098000_42.10.793.3","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20011001)103:2<138::AID-AJMG1529>3.0.CO;2-8"},{"key":"2025101713042098000_42.10.793.4","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.11.1759"},{"key":"2025101713042098000_42.10.793.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00384-4"},{"key":"2025101713042098000_42.10.793.6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.12.2373"},{"key":"2025101713042098000_42.10.793.7","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1212\/WNL.54.5.1103","volume":"54","year":"2000","journal-title":"Neurology"},{"key":"2025101713042098000_42.10.793.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2003.12.052"},{"key":"2025101713042098000_42.10.793.9","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440624"},{"key":"2025101713042098000_42.10.793.10","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001072"},{"key":"2025101713042098000_42.10.793.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00891-5"},{"key":"2025101713042098000_42.10.793.12","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1212\/WNL.57.4.621","volume":"57","year":"2001","journal-title":"Neurology"},{"key":"2025101713042098000_42.10.793.13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1212\/01.WNL.0000042088.22694.E3","volume":"60","year":"2003","journal-title":"Neurology"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2005.033456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T20:04:28Z","timestamp":1760731468000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2005.033456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,20]]},"references-count":13,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2005,9,30]]},"published-print":{"date-parts":[[2005,10]]}},"alternative-id":["10.1136\/jmg.2005.033456"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2005.033456","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,20]]}}}