Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.
Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation.
Crow
Yanick J
YJ
Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds, LS9 7TF, UK. yanickcrow@mac.com
Leitch
Andrea
A
Hayward
Bruce E
BE
Garner
Anna
A
Parmar
Rekha
R
Griffith
Elen
E
Ali
Manir
M
Semple
Colin
C
Aicardi
Jean
J
Babul-Hirji
Riyana
R
Baumann
Clarisse
C
Baxter
Peter
P
Bertini
Enrico
E
Chandler
Kate E
KE
Chitayat
David
D
Cau
Daniel
D
Déry
Catherine
C
Fazzi
Elisa
E
Goizet
Cyril
C
King
Mary D
MD
Klepper
Joerg
J
Lacombe
Didier
D
Lanzi
Giovanni
G
Lyall
Hermione
H
Martínez-Frías
María Luisa
ML
Mathieu
Michèle
M
McKeown
Carole
C
Monier
Anne
A
Oade
Yvette
Y
Quarrell
Oliver W
OW
Rittey
Christopher D
CD
Rogers
R Curtis
RC
Sanchis
Amparo
A
Stephenson
John B P
JB
Tacke
Uta
U
Till
Marianne
M
Tolmie
John L
JL
Tomlin
Pam
P
Voit
Thomas
T
Weschke
Bernhard
B
Woods
C Geoffrey
CG
Lebon
Pierre
P
Bonthron
David T
DT
Ponting
Chris P
CP
Jackson
Andrew P
AP
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D018792:Encephalitis, Viral / Q000151:congenital; D005260:Female; D020271:Heredodegenerative Disorders, Nervous System / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D016914:Ribonuclease H / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
D021122:Protein Subunits; D004247:DNA; C091139:ribonuclease HII; D016914:Ribonuclease H