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

A Richards; AMJM Van Den Maagdenberg; JC Jen; D Kavanagh; P Bertram; D Spitzer; MK Liszewski; ML Barilla-Labarca; GM Terwindt; Y Kasai; M McLellan; MG Grand; KRJ Vanmolkot; B De Vries; J Wan; MJ Kane; H Mamsa; R Schäfer; AH Stam; J Haan; PTVM De Jong; CW Storimans; MJ Van Schooneveld; JA Oosterhuis; A Gschwendter; M Dichgans; KE Kotschet; S Hodgkinson; TA Hardy; MB Delatycki; RA Hajj-Ali; PH Kothari; SF Nelson; RR Frants; RW Baloh; MD Ferrari; JP Atkinson

Journal article

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

A Richards, AMJM Van Den Maagdenberg, JC Jen, D Kavanagh, P Bertram, D Spitzer, MK Liszewski, ML Barilla-Labarca, GM Terwindt, Y Kasai, M McLellan, MG Grand, KRJ Vanmolkot, B De Vries, J Wan, MJ Kane, H Mamsa, R Schäfer, AH Stam, J Haan Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2007

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. © 2007 Nature Publishing Group.