Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE.
Lee-Kirsch
Min Ae
MA
Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, 01307 Dresden, Germany. minae.lee-kirsch@uniklinikum-dresden.de
Gong
Maolian
M
Chowdhury
Dipanjan
D
Senenko
Lydia
L
Engel
Kerstin
K
Lee
Young-Ae
YA
de Silva
Udesh
U
Bailey
Suzanna L
SL
Witte
Torsten
T
Vyse
Timothy J
TJ
Kere
Juha
J
Pfeiffer
Christiane
C
Harvey
Scott
S
Wong
Andrew
A
Koskenmies
Sari
S
Hummel
Oliver
O
Rohde
Klaus
K
Schmidt
Reinhold E
RE
Dominiczak
Anna F
AF
Gahr
Manfred
M
Hollis
Thomas
T
Perrino
Fred W
FW
Lieberman
Judy
J
Hübner
Norbert
N
D020413:3' Untranslated Regions / Q000235:genetics; D011992:Endosomes / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D010750:Phosphoproteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1