학술논문
Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients: Clinical, Neuroimaging and Neuropathological Findings.
Document Type
Report
Author
Alvarez-Mora MI; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Biochemistry and Molecular Genetic Service, Hospital Clínic de Barcelona, 08036 Barcelona, Spain.; Blanco-Palmero VA; Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Quesada-Espinosa JF; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Arteche-Lopez AR; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Llamas-Velasco S; Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Palma Milla C; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Lezana Rosales JM; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Gomez-Manjon I; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Hernandez-Lain A; Neuropathology Unit, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Jimenez Almonacid J; Neuropathology Unit, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Gil-Fournier B; Genetic Service, Hospital Universitario de Getafe, 28905 Madrid, Spain.; Ramiro-León S; Genetic Service, Hospital Universitario de Getafe, 28905 Madrid, Spain.; González-Sánchez M; Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Herrero-San Martín AO; Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Pérez-Martínez DA; Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Gómez-Tortosa E; Neurology Department, Fundación Jiménez Díaz, 28040 Madrid, Spain.; Carro E; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Bartolomé F; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), 28031 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Gomez-Rodriguez MJ; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Network Center for Biomedical Research in Cancer (CIBERONC), 28029 Madrid, Spain.; Sanchez-Calvin MT; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Villarejo-Galende A; Neurology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; Group of Neurodegenerative Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), 28041 Madrid, Spain.; Moreno-Garcia M; Genetic Service, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.; UdisGen-Unidad de Dismorfología y Genética, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
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 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.