Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.
Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.
Rice
Gillian I
GI
Academic Unit of Medical Genetics, University of Manchester, Manchester, UK.
Bond
Jacquelyn
J
Asipu
Aruna
A
Brunette
Rebecca L
RL
Manfield
Iain W
IW
Carr
Ian M
IM
Fuller
Jonathan C
JC
Jackson
Richard M
RM
Lamb
Teresa
T
Briggs
Tracy A
TA
Ali
Manir
M
Gornall
Hannah
H
Couthard
Lydia R
LR
Aeby
Alec
A
Attard-Montalto
Simon P
SP
Bertini
Enrico
E
Bodemer
Christine
C
Brockmann
Knut
K
Brueton
Louise A
LA
Corry
Peter C
PC
Desguerre
Isabelle
I
Fazzi
Elisa
E
Cazorla
Angels Garcia
AG
Gener
Blanca
B
Hamel
Ben C J
BC
Heiberg
Arvid
A
Hunter
Matthew
M
van der Knaap
Marjo S
MS
Kumar
Ram
R
Lagae
Lieven
L
Landrieu
Pierre G
PG
Lourenco
Charles M
CM
Marom
Daphna
D
McDermott
Michael F
MF
van der Merwe
William
W
Orcesi
Simona
S
Prendiville
Julie S
JS
Rasmussen
Magnhild
M
Shalev
Stavit A
SA
Soler
Doriette M
DM
Shinawi
Marwan
M
Spiegel
Ronen
R
Tan
Tiong Y
TY
Vanderver
Adeline
A
Wakeling
Emma L
EL
Wassmer
Evangeline
E
Whittaker
Elizabeth
E
Lebon
Pierre
P
Stetson
Daniel B
DB
Bonthron
David T
DT
Crow
Yanick J
YJ
D019943:Amino Acid Substitution; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000276:immunology; D000076106:SAM Domain and HD Domain-Containing Protein 1
D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins