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Keywords = SorLA immunohistochemistry

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18 pages, 3707 KB  
Case Report
Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer’s Disease Patients: Clinical, Neuroimaging and Neuropathological Findings
by Maria Isabel Alvarez-Mora, Victor Antonio Blanco-Palmero, Juan Francisco Quesada-Espinosa, Ana Rosa Arteche-Lopez, Sara Llamas-Velasco, Carmen Palma Milla, Jose Miguel Lezana Rosales, Irene Gomez-Manjon, Aurelio Hernandez-Lain, Justino Jimenez Almonacid, Belén Gil-Fournier, Soraya Ramiro-León, Marta González-Sánchez, Alejandro Octavio Herrero-San Martín, David Andrés Pérez-Martínez, Estrella Gómez-Tortosa, Eva Carro, Fernando Bartolomé, Maria Jose Gomez-Rodriguez, María Teresa Sanchez-Calvin, Alberto Villarejo-Galende and Marta Moreno-Garciaadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(8), 4230; https://doi.org/10.3390/ijms23084230 - 11 Apr 2022
Cited by 10 | Viewed by 5110
Abstract
In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s 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 [...] Read more.
In the last few years, the SORL1 gene has been strongly implicated in the development of Alzheimer’s 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>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>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. Full article
(This article belongs to the Special Issue Dementia)
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