tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.
Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
Budde
Birgit S
BS
Cologne Center for Genomics and Institute for Genetics, University of Cologne, Cologne, Germany.
Namavar
Yasmin
Y
Barth
Peter G
PG
Poll-The
Bwee Tien
BT
Nürnberg
Gudrun
G
Becker
Christian
C
van Ruissen
Fred
F
Weterman
Marian A J
MA
Fluiter
Kees
K
te Beek
Erik T
ET
Aronica
Eleonora
E
van der Knaap
Marjo S
MS
Höhne
Wolfgang
W
Toliat
Mohammad Reza
MR
Crow
Yanick J
YJ
Steinling
Maja
M
Voit
Thomas
T
Roelenso
Filip
F
Brussel
Wim
W
Brockmann
Knut
K
Kyllerman
Marten
M
Boltshauser
Eugen
E
Hammersen
Gerhard
G
Willemsen
Michèl
M
Basel-Vanagaite
Lina
L
Krägeloh-Mann
Ingeborg
I
de Vries
Linda S
LS
Sztriha
Laszlo
L
Muntoni
Francesco
F
Ferrie
Colin D
CD
Battini
Roberta
R
Hennekam
Raoul C M
RC
Grillo
Eugenio
E
Beemer
Frits A
FA
Stoets
Loes M E
LM
Wollnik
Bernd
B
Nürnberg
Peter
P
Baas
Frank
F
D001921:Brain / Q000378:metabolism; D002531:Cerebellum / Q000002:abnormalities*; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D004722:Endoribonucleases / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011149:Pons / Q000002:abnormalities*; D013577:Syndrome
D004722:Endoribonucleases; C051012:splicing endonuclease