Abstract
We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation co-segregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, N.I.H., Intramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
DNA Mutational Analysis
-
Dementia / genetics*
-
Dementia / metabolism
-
Dementia / physiopathology
-
Disease Progression
-
Exons / genetics*
-
Female
-
Frontal Lobe / metabolism
-
Frontal Lobe / pathology
-
Frontal Lobe / physiopathology
-
Genetic Predisposition to Disease / genetics*
-
Genetic Testing
-
Humans
-
Introns / genetics
-
Male
-
Middle Aged
-
Mutation / genetics*
-
Nerve Tissue Proteins / genetics*
-
PC12 Cells
-
Pedigree
-
RNA Splice Sites / genetics
-
Rats
-
Regulatory Elements, Transcriptional / genetics*
-
Temporal Lobe / metabolism
-
Temporal Lobe / pathology
-
Temporal Lobe / physiopathology
-
tau Proteins
Substances
-
MAPT protein, human
-
Nerve Tissue Proteins
-
RNA Splice Sites
-
tau Proteins