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 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

doi:10.1038/ng2082

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

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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 language	English
Pages (from-to)	1068-1070
Number of pages	3
Journal	Nature Genetics
Volume	39
Issue number	9
DOIs	https://doi.org/10.1038/ng2082
State	Published - Sep 2007

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Richards, A., Van Den Maagdenberg, A. M. J. M., Jen, J. C., Kavanagh, D., Bertram, P., Spitzer, D., Liszewski, M. K., Barilla-Labarca, M. L., Terwindt, G. M., Kasai, Y., McLellan, M., Grand, M. G., Vanmolkot, K. R. J., De Vries, B., Wan, J., Kane, M. J., Mamsa, H., Schäfer, R., Stam, A. H., ... Atkinson, J. P. (2007). C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nature Genetics, 39(9), 1068-1070. https://doi.org/10.1038/ng2082

@article{60da800d28c146f98561d66c6ef6158c,

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

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.",

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

year = "2007",

month = sep,

doi = "10.1038/ng2082",

language = "English",

volume = "39",

pages = "1068--1070",

journal = "Nature Genetics",

issn = "1061-4036",

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Richards, A, Van Den Maagdenberg, AMJM, Jen, JC, Kavanagh, D, Bertram, P, Spitzer, D , Liszewski, MK, Barilla-Labarca, ML, Terwindt, GM, Kasai, Y, McLellan, M, Grand, MG, Vanmolkot, KRJ, De Vries, B, Wan, J, Kane, MJ, Mamsa, H, Schäfer, R, Stam, AH, Haan, J, De Jong, PTVM, Storimans, CW, Van Schooneveld, MJ, Oosterhuis, JA, Gschwendter, A, Dichgans, M, Kotschet, KE, Hodgkinson, S, Hardy, TA, Delatycki, MB, Hajj-Ali, RA, Kothari, PH, Nelson, SF, Frants, RR, Baloh, RW, Ferrari, MD & Atkinson, JP 2007, 'C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy', Nature Genetics, vol. 39, no. 9, pp. 1068-1070. https://doi.org/10.1038/ng2082

TY - JOUR

T1 - C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy

AU - Richards, Anna

AU - Van Den Maagdenberg, Arn M.J.M.

AU - Jen, Joanna C.

AU - Kavanagh, David

AU - Bertram, Paula

AU - Spitzer, Dirk

AU - Liszewski, M. Kathryn

AU - Barilla-Labarca, Maria Louise

AU - Terwindt, Gisela M.

AU - Kasai, Yumi

AU - McLellan, Mike

AU - Grand, Mark Gilbert

AU - Vanmolkot, Kaate R.J.

AU - De Vries, Boukje

AU - Wan, Jijun

AU - Kane, Michael J.

AU - Mamsa, Hafsa

AU - Schäfer, Ruth

AU - Stam, Anine H.

AU - Haan, Joost

AU - De Jong, Paulus T.V.M.

AU - Storimans, Caroline W.

AU - Van Schooneveld, Mary J.

AU - Oosterhuis, Jendo A.

AU - Gschwendter, Andreas

AU - Dichgans, Martin

AU - Kotschet, Katya E.

AU - Hodgkinson, Suzanne

AU - Hardy, Todd A.

AU - Delatycki, Martin B.

AU - Hajj-Ali, Rula A.

AU - Kothari, Parul H.

AU - Nelson, Stanley F.

AU - Frants, Rune R.

AU - Baloh, Robert W.

AU - Ferrari, Michel D.

AU - Atkinson, John P.

PY - 2007/9

Y1 - 2007/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548334617&partnerID=8YFLogxK

U2 - 10.1038/ng2082

DO - 10.1038/ng2082

M3 - Article

C2 - 17660820

AN - SCOPUS:34548334617

SN - 1061-4036

VL - 39

SP - 1068

EP - 1070

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

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

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