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

  • Nat Genet. 2007 Sep;39(9):1068-70. doi: 10.1038/ng2082.
Anna Richards  1 ,  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 Haan ,  Paulus 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
Affiliations
  • 1. Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
PMID: 17660820 DOI: 10.1038/ng2082
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.