Clinical-Genetic Correlations in Familial Alzheimer's Disease Caused by Presenilin 1 Mutations
| Autor: | Fernando Castellanos, Adolfo Jiménez-Huete, Alberto Rábano, Adriano Jimenez-Escrig, Estrella Gómez-Tortosa, Martín Zurdo, M. José Sainz, Eulogio Gil-Neciga, Rosa Guerrero, Sagrario Barquero, Julián Pérez-Pérez, Manuel Baron, Sagrario Manzano, David G. Munoz, Isabel Gobernado |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Biology medicine.disease_cause Presenilin Exon Alzheimer Disease Presenilin-1 medicine Humans Point Mutation Dementia Prospective Studies Aged Genetics Mutation General Neuroscience Parkinsonism Point mutation Electroencephalography Exons General Medicine Middle Aged medicine.disease Pedigree Psychiatry and Mental health Clinical Psychology Phenotype Female Geriatrics and Gerontology medicine.symptom Age of onset Myoclonus |
| Zdroj: | Journal of Alzheimer's Disease. 19:873-884 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-2010-1292 |
| Popis: | We describe the clinical phenotype of nine kindred with presenile Alzheimer's disease (AD) caused by different presenilin 1 (PS1) point mutations, and compare them with reported families with mutations in the same codons. Mutations were in exon 4 (Phe105Val), exon 5 (Pro117Arg, Glu120Gly), exon 6 (His163Arg), exon 7 (Leu226Phe), exon 8 (Val261Leu, Val272Ala, Leu282Arg), and exon 12 (Ile439Ser). Three of these amino acid changes (Phe105Val, Glu120Gly, and Ile439Ser) had not been previously reported. Distinct clinical features, including age of onset, symptoms and signs associated with the cortical-type dementia and aggressiveness of the disease, characterized the different mutations and were quite homogeneous across family members. Age of onset fell within a consistent range: some mutations caused the disease in the thirties (P117R, L226F, V272A), other in the forties (E120G, H163R, V261L, L282R), and other in the fifties (F105V, I439S). Associated features also segregated with specific mutations: early epileptic activity (E120G), spastic paraparesis (V261L), subcortical dementia and parkinsonism (V272A), early language impairment, frontal signs, and myoclonus (L226F), and late myoclonus and seizures (H163R, L282R). Neurological deterioration was particularly aggressive in PS1 mutations with earlier age of onset such as P117R, L226F, and E120G. With few exceptions, a similar clinical phenotype was found in families reported to have either the same mutation or different amino acid changes in the same codons. This series points to a strong influence of the specific genetic defect in the development of the clinical phenotype. |
| Databáze: | OpenAIRE |
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