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.
Richards
Anna
A
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
van den Maagdenberg
Arn M J M
AM
Jen
Joanna C
JC
Kavanagh
David
D
Bertram
Paula
P
Spitzer
Dirk
D
Liszewski
M Kathryn
MK
Barilla-Labarca
Maria-Louise
ML
Terwindt
Gisela M
GM
Kasai
Yumi
Y
McLellan
Mike
M
Grand
Mark Gilbert
MG
Vanmolkot
Kaate R J
KR
de Vries
Boukje
B
Wan
Jijun
J
Kane
Michael J
MJ
Mamsa
Hafsa
H
Schäfer
Ruth
R
Stam
Anine H
AH
Haan
Joost
J
de Jong
Paulus T V M
PT
Storimans
Caroline W
CW
van Schooneveld
Mary J
MJ
Oosterhuis
Jendo A
JA
Gschwendter
Andreas
A
Dichgans
Martin
M
Kotschet
Katya E
KE
Hodgkinson
Suzanne
S
Hardy
Todd A
TA
Delatycki
Martin B
MB
Hajj-Ali
Rula A
RA
Kothari
Parul H
PH
Nelson
Stanley F
SF
Frants
Rune R
RR
Baloh
Robert W
RW
Ferrari
Michel D
MD
Atkinson
John P
JP
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