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 Schaefer, Anine H. Stam, Joost HaanT. V. M. de Jong Paulus, 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*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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
    Publication statusPublished - Sep-2007

    Keywords

    • AICARDI-GOUTIERES-SYNDROME
    • CEREBRORETINAL VASCULOPATHY
    • HEREDITARY ENDOTHELIOPATHY
    • VASCULAR RETINOPATHY
    • NEPHROPATHY
    • LOCUS

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