{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:53:00Z","timestamp":1769161980709,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,6,28]],"date-time":"2008-06-28T00:00:00Z","timestamp":1214611200000},"content-version":"vor","delay-in-days":3680,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[1998,6]]},"abstract":"<jats:p>Most of the cases of early\u2010onset familial Alzheimer's disease (FAD) are related to missense mutations in the presenilin 1 (PS\u20101) gene on chromosome 14. Although PS\u20101 mutations are distributed throughout the entire open reading frame, most mutations are found in transmembrane region II and hydrophilic loop VI encoded by exons 5 and 8, respectively. These two groups of substitutions are associated with an age of onset of 40\u201343 years for exon 5 and 45\u201355 years for exon 8, respectively. We have previously described a South American pedigree from Argentina with early\u2010onset FAD (mean age of onset 38.9 \u00b1 3.9 years) with no mutations in exons 16 and 17 of the \u03b2\u2010protein precursor gene (\u03b2PP<jats:sub>770<\/jats:sub> transcript). Here we report the identification of an A\u00b1T transversion at the first position of codon 146 of PS\u20101 in these patients. This missense mutation results in a Met \u00b1 Leu substitution, as reported for the Italian pedigrees Tor 1.1 and FAD4. The significant differences in ages of onset and death among members of generations II\u2014III and IV suggest that other genetic and\/or environmental factors may influence disease phenotype in this pedigree.<\/jats:p>","DOI":"10.1111\/j.1399-0004.1998.tb02597.x","type":"journal-article","created":{"date-parts":[[2010,7,19]],"date-time":"2010-07-19T09:52:22Z","timestamp":1279533142000},"page":"469-473","source":"Crossref","is-referenced-by-count":23,"title":["Presenilin 1 Met146Leu variant due to an A&amp;T transversion in an early\u2010onset familial Alzheimer's disease pedigree from Argentina"],"prefix":"10.1111","volume":"53","author":[{"given":"Laura","family":"Morelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda I.","family":"Prat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efrat","family":"Levy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos A.","family":"Mangone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo M.","family":"Casta\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"e_1_2_1_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(84)91209-9"},{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/375754a0"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7638622"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.12.2373"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199602290-00029"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.Supplement_1.1449"},{"key":"e_1_2_1_8_2","first-page":"91","article-title":"The presenilin genes and their role in early\u2010onset familial Alzheimer's disease","volume":"1","author":"Tanzi RE","year":"1996","journal-title":"Alzheimer's Dis Rev"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1995.tb05835.x"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/3.9.2303"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92823-K"},{"key":"e_1_2_1_13_2","first-page":"113","article-title":"Detection and quantitation of amyloid \u03b2\u2010peptide with 2 monoclonal antibodies","volume":"7","author":"Kim KS","year":"1990","journal-title":"Neurosci Res Commun"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1996.tb02375.x"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-230"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91728-5"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)11100-W"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-219"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)01030-2"},{"issue":"3","key":"e_1_2_1_20_2","first-page":"194","article-title":"Demence presenile d'Alzheimer transmise dans une famille etendue","volume":"141","author":"Foncin J\u2010F","year":"1985","journal-title":"Rev Neurol (Paris)"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.3.491"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.1998.tb02597.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.1998.tb02597.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T08:11:06Z","timestamp":1698480666000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.1998.tb02597.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,6]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1998,6]]}},"alternative-id":["10.1111\/j.1399-0004.1998.tb02597.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.1998.tb02597.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,6]]}}}