C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy by Richards Anna, van den Maagdenberg Arn M J M, Jen Joanna C, Kavanagh David, Bertram Paula, Spitzer Dirk, Liszewski M Kathryn, Barilla-Labarca Maria-Louise, Terwindt Gisela M, Kasai Yumi, McLellan Mike, Grand Mark Gilbert, Vanmolkot Kaate R J, de Vries Boukje, Wan Jijun, Kane Michael J, Mamsa Hafsa, Schäfer Ruth, Stam Anine H, Haan Joost, de Jong Paulus T V M, Storimans Caroline W, van Schooneveld Mary J, Oosterhuis Jendo A, Gschwendter Andreas, Dichgans Martin, Kotschet Katya E, Hodgkinson Suzanne, Hardy Todd A, Delatycki Martin B, Hajj-Ali Rula A, Kothari Parul H, Nelson Stanley F, Frants Rune R, Baloh Robert W, Ferrari Michel D, Atkinson John P in Nature genetics (2007). PubMed

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.

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