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A random Abstract
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Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome.
[pendred syndrome]
Mutations
in
SLC
26
A
4
cause
nonsyndromic
hearing
loss
associated
with
an
enlarged
vestibular
aqueduct
(
EVA
,
also
known
as
DFNB
4
)
and
Pendred
syndrome
(
PS
)
,
the
most
common
type
of
autosomal-recessive
syndromic
deafness
.
In
many
patients
with
an
EVA
/
PS
phenotype
,
mutation
screening
of
SLC
26
A
4
fails
to
identify
two
disease-causing
allele
variants
.
That
a
sizable
fraction
of
patients
carry
only
one
SLC
26
A
4
mutation
suggests
that
EVA
/
PS
is
a
complex
disease
involving
other
genetic
factors
.
Here
,
we
show
that
mutations
in
the
inwardly
rectifying
K
(
+
)
channel
gene
KCNJ
10
are
associated
with
nonsyndromic
hearing
loss
in
carriers
of
SLC
26
A
4
mutations
with
an
EVA
/
PS
phenotype
.
In
probands
from
two
families
,
we
identified
double
heterozygosity
in
affected
individuals
.
These
persons
carried
single
mutations
in
both
SLC
26
A
4
and
KCNJ
10
.
The
identified
SLC
26
A
4
mutations
have
been
previously
implicated
in
EVA
/
PS
,
and
the
KCNJ
10
mutations
reduce
K
(
+
)
conductance
activity
,
which
is
critical
for
generating
and
maintaining
the
endocochlear
potential
.
In
addition
,
we
show
that
haploinsufficiency
of
Slc
26
a
4
in
the
Slc
26
a
4
(
+
/
-
)
mouse
mutant
results
in
reduced
protein
expression
of
Kcnj
10
in
the
stria
vascularis
of
the
inner
ear
.
Our
results
link
KCNJ
10
mutations
with
EVA
/
PS
and
provide
further
support
for
the
model
of
EVA
/
PS
as
a
multigenic
complex
disease
.