C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy

Anna Richards, Arn M.J.M. Van Den Maagdenberg, Joanna C. Jen, David Kavanagh, Paula Bertram, Dirk Spitzer, M. Kathryn Liszewski, Maria Louise Barilla-Labarca, Gisela M. Terwindt, Yumi Kasai, Mike McLellan, Mark Gilbert Grand, Kaate R.J. Vanmolkot, Boukje De Vries, Jijun Wan, Michael J. Kane, Hafsa Mamsa, Ruth Schäfer, Anine H. Stam, Joost HaanPaulus T.V.M. De Jong, Caroline W. Storimans, Mary J. Van Schooneveld, Jendo A. Oosterhuis, Andreas Gschwendter, Martin Dichgans, Katya E. Kotschet, Suzanne Hodgkinson, Todd A. Hardy, Martin B. Delatycki, Rula A. Hajj-Ali, Parul H. Kothari, Stanley F. Nelson, Rune R. Frants, Robert W. Baloh, Michel D. Ferrari, John P. Atkinson

Research output: Contribution to journalArticlepeer-review

343 Scopus citations

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.

Original languageEnglish
Pages (from-to)1068-1070
Number of pages3
JournalNature Genetics
Volume39
Issue number9
DOIs
StatePublished - Sep 2007

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