Abstract
Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias.
Publication types
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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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Amino Acid Sequence
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Brain Diseases / enzymology
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Brain Diseases / genetics*
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Cell Line
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Cell Nucleus / metabolism
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Cytoplasm / metabolism
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Exodeoxyribonucleases / chemistry
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Exodeoxyribonucleases / genetics*
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Exodeoxyribonucleases / metabolism
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Genes, Dominant
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Genetic Predisposition to Disease
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Humans
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Microscopy, Confocal
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Molecular Sequence Data
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Mutation*
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Phosphoproteins / chemistry
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Phosphoproteins / genetics*
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Phosphoproteins / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Retinal Diseases / enzymology
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Retinal Diseases / genetics*
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Sequence Homology, Amino Acid
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Transfection
Substances
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Luminescent Proteins
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Phosphoproteins
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Recombinant Fusion Proteins
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Exodeoxyribonucleases
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three prime repair exonuclease 1