Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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A Drosophila mutant of LETM1, a candidate gene for seizures in Wolf-Hirschhorn syndrome.
[wolf-hirschhorn syndrome]
Human
Wolf-
Hirschhorn
syndrome
(
WHS
)
is
a
multigenic
disorder
resulting
from
a
hemizygous
deletion
on
chromosome
4
.
LETM
1
is
the
best
candidate
gene
for
seizures
,
the
strongest
haploinsufficiency
phenotype
of
WHS
patients
.
Here
,
we
identify
the
Drosophila
gene
CG
4589
as
the
ortholog
of
LETM
1
and
name
the
gene
DmLETM
1
.
Using
RNA
interference
approaches
in
both
Drosophila
melanogaster
cultured
cells
and
the
adult
fly
,
we
have
assayed
the
effects
of
down-regulating
the
LETM
1
gene
on
mitochondrial
function
.
We
also
show
that
DmLETM
1
complements
growth
and
mitochondrial
K
(
+
)
/
H
(
+
)
exchange
(
KHE
)
activity
in
yeast
deficient
for
LETM
1
.
Genetic
studies
allowing
the
conditional
inactivation
of
LETM
1
function
in
specific
tissues
demonstrate
that
the
depletion
of
DmLETM
1
results
in
roughening
of
the
adult
eye
,
mitochondrial
swelling
and
developmental
lethality
in
third
-instar
larvae
,
possibly
the
result
of
deregulated
mitophagy
.
Neuronal
specific
down-regulation
of
DmLETM
1
results
in
impairment
of
locomotor
behavior
in
the
fly
and
reduced
synaptic
neurotransmitter
release
.
Taken
together
our
results
demonstrate
the
function
of
DmLETM
1
as
a
mitochondrial
osmoregulator
through
its
KHE
activity
and
uncover
a
pathophysiological
WHS
phenotype
in
the
model
organism
D
.
melanogaster
.
