1. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy.
- Author
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Richards A, van den Maagdenberg AM, Jen JC, Kavanagh D, Bertram P, Spitzer D, Liszewski MK, Barilla-Labarca ML, Terwindt GM, Kasai Y, McLellan M, Grand MG, Vanmolkot KR, de Vries B, Wan J, Kane MJ, Mamsa H, Schäfer R, Stam AH, Haan J, de Jong PT, Storimans CW, van Schooneveld MJ, Oosterhuis JA, Gschwendter A, Dichgans M, Kotschet KE, Hodgkinson S, Hardy TA, Delatycki MB, Hajj-Ali RA, Kothari PH, Nelson SF, Frants RR, Baloh RW, Ferrari MD, and Atkinson JP
- Subjects
- Amino Acid Sequence, Brain Diseases enzymology, Cell Line, Cell Nucleus metabolism, Cytoplasm metabolism, Exodeoxyribonucleases chemistry, Exodeoxyribonucleases metabolism, Genes, Dominant, Genetic Predisposition to Disease, Humans, Luminescent Proteins genetics, Luminescent Proteins metabolism, Microscopy, Confocal, Molecular Sequence Data, Phosphoproteins chemistry, Phosphoproteins metabolism, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Retinal Diseases enzymology, Sequence Homology, Amino Acid, Transfection, Brain Diseases genetics, Exodeoxyribonucleases genetics, Mutation, Phosphoproteins genetics, Retinal Diseases genetics
- 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.
- Published
- 2007
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