{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:09:52Z","timestamp":1790467792810,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/01067"],"award-info":[{"award-number":["PI17\/01067"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CM 18\/0095"],"award-info":[{"award-number":["CM 18\/0095"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["JR 18\/00046"],"award-info":[{"award-number":["JR 18\/00046"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Agency for Administration of University and Research","doi-asserted-by":"publisher","award":["2017SGR1134"],"award-info":[{"award-number":["2017SGR1134"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer\u2019s disease (AD). We performed whole-exome sequencing on 37 patients with early-onset dementia or family history suggestive of autosomal dominant dementia. Data analysis was based on a custom panel that included 46 genes related to AD and dementia. SORL1 variants were present in a high proportion of patients with candidate variants (15%, 3\/20). We expand the clinical manifestations associated with the SORL1 gene by reporting detailed clinical and neuroimaging findings of six unrelated patients with AD and SORL1 mutations. We also present for the first time a patient with the homozygous truncating variant c.364C&gt;T (p.R122*) in SORL1, who also had severe cerebral amyloid angiopathy. Furthermore, we report neuropathological findings and immunochemistry assays from one patient with the splicing variant c.4519+5G&gt;A in the SORL1 gene, in which AD was confirmed by neuropathological examination. Our results highlight the heterogeneity of clinical presentation and familial dementia background of SORL1-associated AD and suggest that SORL1 might be contributing to AD development as a risk factor gene rather than as a major autosomal dominant gene.<\/jats:p>","DOI":"10.3390\/ijms23084230","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:23:11Z","timestamp":1649722991000},"page":"4230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer\u2019s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-8915","authenticated-orcid":false,"given":"Maria Isabel","family":"Alvarez-Mora","sequence":"first","affiliation":[{"name":"Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"},{"name":"Biochemistry and Molecular Genetic Service, Hospital Cl\u00ednic de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1721-6217","authenticated-orcid":false,"given":"Victor Antonio","family":"Blanco-Palmero","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"},{"name":"Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain"},{"name":"Group of Neurodegenerative Diseases, Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Francisco","family":"Quesada-Espinosa","sequence":"additional","affiliation":[{"name":"Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"},{"name":"UdisGen\u2014Unidad de Dismorfolog\u00eda y Gen\u00e9tica, Hospital Universitario 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