Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients : Clinical, Neuroimaging and Neuropathological Findings
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
International journal of molecular sciences - 23(2022), 8 vom: 11. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alvarez-Mora, Maria Isabel [VerfasserIn] |
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| Links: |
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| Themen: |
Alzheimer |
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| Anmerkungen: |
Date Completed 26.04.2022 Date Revised 08.03.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms23084230 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339862246 |
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| 100 | 1 | |a Alvarez-Mora, Maria Isabel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Heterozygous and Homozygous Variants in SORL1 Gene in Alzheimer's Disease Patients |b Clinical, Neuroimaging and Neuropathological Findings |
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| 500 | |a Date Completed 26.04.2022 | ||
| 500 | |a Date Revised 08.03.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Alzheimer | |
| 650 | 4 | |a SORL1 | |
| 650 | 4 | |a SorLA immunohistochemistry | |
| 650 | 4 | |a cerebral amyloid angiopathy | |
| 650 | 4 | |a homozygous case | |
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| 700 | 1 | |a Blanco-Palmero, Victor Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Quesada-Espinosa, Juan Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Arteche-Lopez, Ana Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Llamas-Velasco, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Palma Milla, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Lezana Rosales, Jose Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez-Manjon, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Hernandez-Lain, Aurelio |e verfasserin |4 aut | |
| 700 | 1 | |a Jimenez Almonacid, Justino |e verfasserin |4 aut | |
| 700 | 1 | |a Gil-Fournier, Belén |e verfasserin |4 aut | |
| 700 | 1 | |a Ramiro-León, Soraya |e verfasserin |4 aut | |
| 700 | 1 | |a González-Sánchez, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Herrero-San Martín, Alejandro Octavio |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez-Martínez, David Andrés |e verfasserin |4 aut | |
| 700 | 1 | |a Gómez-Tortosa, Estrella |e verfasserin |4 aut | |
| 700 | 1 | |a Carro, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Bartolomé, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Gomez-Rodriguez, Maria Jose |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez-Calvin, María Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Villarejo-Galende, Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno-Garcia, Marta |e verfasserin |4 aut | |
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