Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome.
[kabuki syndrome]
Kabuki
syndrome
is
caused
by
haploinsufficiency
for
either
of
two
genes
that
promote
the
opening
of
chromatin
.
If
an
imbalance
between
open
and
closed
chromatin
is
central
to
the
pathogenesis
of
Kabuki
syndrome
,
agents
that
promote
chromatin
opening
might
have
therapeutic
potential
.
We
have
characterized
a
mouse
model
of
Kabuki
syndrome
with
a
heterozygous
deletion
in
the
gene
encoding
the
lysine-
specific
methyltransferase
2
D
(
Kmt
2
d
)
,
leading
to
impairment
of
methyltransferase
function
.
In
vitro
reporter
alleles
demonstrated
a
reduction
in
histone
4
acetylation
and
histone
3
lysine
4
trimethylation
(
H
3
K
4
me
3
)
activity
in
mouse
embryonic
fibroblasts
from
Kmt
2
d
(
+
/
βGeo
)
mice
.
These
activities
were
normalized
in
response
to
AR
-
42
,
a
histone
deacetylase
inhibitor
.
In
vivo
,
deficiency
of
H
3
K
4
me
3
in
the
dentate
gyrus
granule
cell
layer
of
Kmt
2
d
(
+
/
βGeo
)
mice
correlated
with
reduced
neurogenesis
and
hippocampal
memory
defects
.
These
abnormalities
improved
upon
postnatal
treatment
with
AR
-
42
.
Our
work
suggests
that
a
reversible
deficiency
in
postnatal
neurogenesis
underlies
intellectual
disability
in
Kabuki
syndrome
.
Diseases
Validation
Diseases presenting
"intellectual disability"
symptom
22q11.2 deletion syndrome
alexander disease
alpha-thalassemia
aniridia
child syndrome
cohen syndrome
cowden syndrome
hirschsprung disease
homocystinuria without methylmalonic aciduria
hydrocephalus with stenosis of the aqueduct of sylvius
kabuki syndrome
kallmann syndrome
monosomy 21
oculocutaneous albinism
oligodontia
phenylketonuria
proteus syndrome
triple a syndrome
wolf-hirschhorn syndrome
This symptom has already been validated