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

被引：323

作者：

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

Schaefer, Ruth

Stam, Anine H.

Haan, Joost

Paulus, T. V. M. de Jong

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. ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63110 USA

[2] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands

[3] Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands

[4] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA

[5] N Shore Long Isl Jewish Hlth Syst, Dept Med, Div Rheumatol, Manhasset, NY 11030 USA

[6] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63110 USA

[7] Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA

[8] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Dept Ophthalmogenet, NL-1000 GC Amsterdam, Netherlands

[9] Acad Med Ctr, Dept Ophthalmol, NL-1100 DD Amsterdam, Netherlands

[10] Erasmus MC, Dept Epidemiol & Biostat, NL-3000 CA Rotterdam, Netherlands

[11] Meander Med Ctr, NL-3800 BM Amersfoort, Netherlands

[12] Univ Med Ctr, Dept Ophthalmol, NL-3508 GA Utrecht, Netherlands

[13] Leiden Univ, Med Ctr, Dept Ophthalmol, NL-2300 RC Leiden, Netherlands

[14] Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81377 Munich, Germany

[15] Monash Med Ctr, Dept Neurol, Clayton, Vic 3168, Australia

[16] Liverpool Hosp, Dept Neurol, Liverpool, NSW 2170, Australia

[17] Concord Repatriat Gen Hosp, Dept Neurol, Concord, NSW 2139, Australia

[18] Bruce Lefroy Ctr Genet Hlth Res, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia

[19] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Parkville, Vic 3052, Australia

[20] Cleveland Clin Fdn, Dept Rheumat & Immunol Dis, Cleveland, OH 44195 USA

[21] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

来源：

NATURE GENETICS | 2007年 / 39卷 / 09期

关键词：

D O I：

10.1038/ng2082

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1068 / 1070

页数：3

共 15 条

[1] The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death [J].