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.
Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, 01307 Dresden, Germany. minae.lee-kirsch@uniklinikum-dresden.de
Min Ae
MA
Lee-Kirsch
Maolian
M
Gong
Dipanjan
D
Chowdhury
Lydia
L
Senenko
Kerstin
K
Engel
Young-Ae
YA
Lee
Udesh
U
de Silva
Suzanna L
SL
Bailey
Torsten
T
Witte
Timothy J
TJ
Vyse
Juha
J
Kere
Christiane
C
Pfeiffer
Scott
S
Harvey
Andrew
A
Wong
Sari
S
Koskenmies
Oliver
O
Hummel
Klaus
K
Rohde
Reinhold E
RE
Schmidt
Anna F
AF
Dominiczak
Manfred
M
Gahr
Thomas
T
Hollis
Fred W
FW
Perrino
Judy
J
Lieberman
Norbert
N
Hübner
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