Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
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
.
Diseases
Validation
Diseases presenting
"hearing loss"
symptom
22q11.2 deletion syndrome
achondroplasia
adrenomyeloneuropathy
alexander disease
benign recurrent intrahepatic cholestasis
canavan disease
cohen syndrome
congenital toxoplasmosis
dentinogenesis imperfecta
fabry disease
familial mediterranean fever
heparin-induced thrombocytopenia
hirschsprung disease
holt-oram syndrome
homocystinuria without methylmalonic aciduria
hydrocephalus with stenosis of the aqueduct of sylvius
kabuki syndrome
kallmann syndrome
neonatal adrenoleukodystrophy
pendred syndrome
von hippel-lindau disease
wolf-hirschhorn syndrome
This symptom has already been validated