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A random Abstract
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Identification of allelic variants of pendrin (SLC26A4) with loss and gain of function.
[pendred syndrome]
Pendrin
is
a
multifunctional
anion
transporter
that
exchanges
chloride
and
iodide
in
the
thyroid
,
as
well
as
chloride
and
bicarbonate
in
the
inner
ear
,
kidney
and
airways
.
Loss
or
reduction
in
the
function
of
pendrin
results
in
both
syndromic
(
Pendred
syndrome
)
and
non-syndromic
(
non-syndromic
enlarged
vestibular
aqueduct
(
ns-
EVA
)
)
hearing
loss
.
Factors
inducing
an
up-regulation
of
pendrin
in
the
kidney
and
the
lung
may
have
an
impact
on
the
pathogenesis
of
hypertension
,
chronic
obstructive
pulmonary
disease
(
COPD
)
and
asthma
.
Here
we
characterize
the
ion
transport
activity
of
wild-
type
(
WT
)
pendrin
and
seven
of
its
allelic
variants
selected
among
those
reported
in
the
single
nucleotide
polymorphisms
data
base
(
dbSNPs
)
,
some
of
which
were
previously
identified
in
a
cohort
of
individuals
with
normal
hearing
or
deaf
patients
belonging
to
the
Spanish
population
.
WT
and
mutated
pendrin
allelic
variants
were
functionally
characterized
in
a
heterologous
over-expression
system
by
means
of
fluorometric
methods
evaluating
the
I
(
-
)
/
Cl
(
-
)
and
Cl
(
-
)
/
OH
(
-
)
exchange
and
an
assay
evaluating
the
efflux
of
radiolabeled
iodide
.
The
transport
activity
of
pendrin
P
70
L
,
P
301
L
and
F
667
C
is
completely
abolished
;
pendrin
V
609
G
and
D
687
Y
allelic
variants
are
functionally
impaired
but
retain
significant
transport
.
Pendrin
F
3
54
S
activity
is
indistinguishable
from
WT
,
while
pendrin
V
88
I
and
G
740
S
exhibit
a
gain
of
function
.
Amino
acid
substitutions
involving
a
proline
always
result
in
a
severe
loss
of
function
of
pendrin
.
Two
hyperfunctional
allelic
variants
(
V
88
I
,
G
740
S
)
have
been
identified
,
and
they
may
have
a
contributing
role
in
the
pathogenesis
of
hypertension
,
COPD
and
asthma
.
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
