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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2008-5-26
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0304-3940
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
438
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
257-9
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pubmed:dateRevised |
2011-6-13
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pubmed:meshHeading |
pubmed-meshheading:18479822-Adult,
pubmed-meshheading:18479822-Alzheimer Disease,
pubmed-meshheading:18479822-Amino Acid Substitution,
pubmed-meshheading:18479822-Amyloid beta-Peptides,
pubmed-meshheading:18479822-Brain,
pubmed-meshheading:18479822-Cell Line,
pubmed-meshheading:18479822-Chromosome Disorders,
pubmed-meshheading:18479822-DNA Mutational Analysis,
pubmed-meshheading:18479822-Disease Progression,
pubmed-meshheading:18479822-Female,
pubmed-meshheading:18479822-Gene Frequency,
pubmed-meshheading:18479822-Genes, Dominant,
pubmed-meshheading:18479822-Genetic Markers,
pubmed-meshheading:18479822-Genetic Predisposition to Disease,
pubmed-meshheading:18479822-Genetic Testing,
pubmed-meshheading:18479822-Genotype,
pubmed-meshheading:18479822-Humans,
pubmed-meshheading:18479822-Male,
pubmed-meshheading:18479822-Pedigree,
pubmed-meshheading:18479822-Peptide Fragments,
pubmed-meshheading:18479822-Point Mutation,
pubmed-meshheading:18479822-Polymorphism, Genetic,
pubmed-meshheading:18479822-Presenilin-1
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pubmed:year |
2008
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pubmed:articleTitle |
Novel presenilin 1 variant (P117A) causing Alzheimer's disease in the fourth decade of life.
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pubmed:affiliation |
Department of Psychiatry, Washington University School of Medicine, United States.
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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