Abstract
Over 160 rare genetic variants in presenilin 1 (PSEN1) are known to cause Alzheimer's disease (AD). In this study we screened a family with early-onset AD for mutations in PSEN1 using direct DNA sequencing. We identified a novel PSEN1 genetic variant which results in the substitution of a Proline with an Alanine at codon 117 (P117A). The P117A variant was present in all demented individuals and fifty percent of at risk individuals. This variant occurs at a site where three other disease-causing variants have been previously observed. In vitro functional studies demonstrate that the P117A variant results in an altered Abeta42/total Abeta ratio consistent with an AD causing mutation. The P117A variant is a novel mutation in PSEN1, which causes early-onset AD in an autosomal dominant manner.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Alzheimer Disease / genetics*
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Alzheimer Disease / physiopathology
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Amino Acid Substitution / genetics
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Amyloid beta-Peptides / genetics
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Brain / metabolism*
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Brain / physiopathology
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Cell Line
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Chromosome Disorders / genetics
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DNA Mutational Analysis
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Disease Progression
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Female
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Gene Frequency
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Genes, Dominant / genetics
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Genetic Markers / genetics
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Genetic Predisposition to Disease / genetics*
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Genetic Testing
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Genotype
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Humans
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Male
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Pedigree
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Peptide Fragments / genetics
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Point Mutation / genetics
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Polymorphism, Genetic / genetics*
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Presenilin-1 / biosynthesis
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Presenilin-1 / genetics*
Substances
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Amyloid beta-Peptides
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Genetic Markers
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Peptide Fragments
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Presenilin-1
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amyloid beta-protein (1-42)