{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:18:06Z","timestamp":1777594686647,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG051218"],"award-info":[{"award-number":["U01AG051218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in three genes (<jats:italic>APP, PSEN1,<\/jats:italic> and <jats:italic>PSEN2<\/jats:italic>) are the main cause of the autosomal dominant early\u2010onset Alzheimer's disease (AD\u2010EOAD). In <jats:italic>PSEN1,<\/jats:italic> the A431E (c.1292C&gt;A, rs63750083) mutation is suspected to have exerted a founder effect in the State of Jalisco, Mexico. In Guadalajara, Jalisco, Mexico, this mutation was found in 46 index cases evaluated for AD\u2010EOAD. In our genealogical analysis, 301 affected relatives of the mutation carriers were identified, 195 of whom were already deceased at the time of interview. Moreover, 560 descendants had a 50% risk of carrying the mutation, and 348 were potentially at risk. A systematic phenotyping was performed in 39 patients. The mean onset age was 42.5\u2009\u00b1\u20093.9\u2009years, and no significant difference in onset age was observed between the male and female patients. Furthermore, a substantial clinical heterogeneity and high frequencies of spastic paraparesis, language disorders, and neuropsychiatric symptoms were observed. To our knowledge, the investigated families represent the second biggest population carrying a <jats:italic>PSEN1<\/jats:italic> mutation in Latin America, offering a unique opportunity to study the genetic basis of Alzheimer's disease. Addressing AD\u2010EOAD warrants an integral approach involving a deep understanding of its clinical behavior, as well as counseling protocols and prevention studies.<\/jats:p>","DOI":"10.1002\/ajmg.c.31865","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T09:04:01Z","timestamp":1607072641000},"page":"1023-1029","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Autosomal dominant early onset Alzheimer's disease in the Mexican state of Jalisco: High frequency of the mutation <scp><i>PSEN1<\/i><\/scp> c.<scp>1292C<\/scp>&gt;A and phenotypic profile of patients"],"prefix":"10.1002","volume":"184","author":[{"given":"Sofia","family":"Dumois\u2010Petersen","sequence":"first","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, IMSS  Guadalajara Jalisco Mexico"},{"name":"Doctorado en Gen\u00e9tica Humana CUCS\u2010UdeG  Guadalajara Jalisco Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha P.","family":"Gallegos\u2010Arreola","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, IMSS  Guadalajara Jalisco Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda T.","family":"Maga\u00f1a\u2010Torres","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, IMSS  Guadalajara Jalisco Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco J.","family":"Perea\u2010D\u00edaz","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, IMSS  Guadalajara Jalisco Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Ringman","sequence":"additional","affiliation":[{"name":"Department of Neurology Keck School of Medicine at USC  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-4579","authenticated-orcid":false,"given":"Luis E.","family":"Figuera","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n de Gen\u00e9tica Centro de Investigaci\u00f3n Biom\u00e9dica de Occidente, IMSS  Guadalajara Jalisco Mexico"},{"name":"Doctorado en Gen\u00e9tica Humana CUCS\u2010UdeG  Guadalajara Jalisco Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0611-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.18.2257"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00115-005-1949-y"},{"issue":"32","key":"e_1_2_9_6_1","first-page":"151","article-title":"Corredores y circuitos que estructuran la regi\u00f3n de Los Altos de Jalisco","author":"Camarena Luhrs M.","year":"2005","journal-title":"Espiral, Estudios Sobre Estado Y Sociedad"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.96"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.12.2.233"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002270"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1424"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.56"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000687"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-006-0053-1"},{"key":"e_1_2_9_14_1","unstructured":"Mutations Database. (n.d.)Alzforum. Retrieved November 26 2019 fromhttp:\/\/www.alzforum.org\/mutations."},{"key":"e_1_2_9_15_1","unstructured":"National Center for Biotechnology Information. (n.d.). ClinVar [VCV000018155.3]. Accessed Oct. 15 2020 fromhttps:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/VCV000018155.3)."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10636"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-5-2"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1385\/NMM:2:1:01"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30193-4"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-120907"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618657114"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-006-0043-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2305-5839.2015.01.19"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0487-5"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.31865","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.c.31865","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.31865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T14:57:25Z","timestamp":1731423445000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.31865"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/ajmg.c.31865"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.31865","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"value":"1552-4868","type":"print"},{"value":"1552-4876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"2020-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}