C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy.
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.
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Anna
A
Richards
Arn M J M
AM
van den Maagdenberg
Joanna C
JC
Jen
David
D
Kavanagh
Paula
P
Bertram
Dirk
D
Spitzer
M Kathryn
MK
Liszewski
Maria-Louise
ML
Barilla-Labarca
Gisela M
GM
Terwindt
Yumi
Y
Kasai
Mike
M
McLellan
Mark Gilbert
MG
Grand
Kaate R J
KR
Vanmolkot
Boukje
B
de Vries
Jijun
J
Wan
Michael J
MJ
Kane
Hafsa
H
Mamsa
Ruth
R
Schäfer
Anine H
AH
Stam
Joost
J
Haan
Paulus T V M
PT
de Jong
Caroline W
CW
Storimans
Mary J
MJ
van Schooneveld
Jendo A
JA
Oosterhuis
Andreas
A
Gschwendter
Martin
M
Dichgans
Katya E
KE
Kotschet
Suzanne
S
Hodgkinson
Todd A
TA
Hardy
Martin B
MB
Delatycki
Rula A
RA
Hajj-Ali
Parul H
PH
Kothari
Stanley F
SF
Nelson
Rune R
RR
Frants
Robert W
RW
Baloh
Michel D
MD
Ferrari
John P
JP
Atkinson
D000595:Amino Acid Sequence; D001927:Brain Diseases / Q000201:enzymology / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012164:Retinal Diseases / Q000201:enzymology / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D008164:Luminescent Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1