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A novel cysteine-sparing NOTCH3 mutation in a Chinese family with CADASIL.
[cadasil]
Cerebral
autosomal
dominant
arteriopathy
with
subcortical
infarcts
and
leukoencephalopathy
(
CADASIL
)
is
an
adult
onset
cerebral
small
vessel
disorder
caused
by
the
mutations
of
the
neurogenic
locus
notch
homolog
protein
3
(
NOTCH
3
)
gene
.
The
extracellular
part
of
NOTCH
3
is
composed
of
34
epidermal
growth
factor
-like
(
EGF
-like
)
repeat
domains
.
Each
EGF
-like
domain
is
rich
of
cysteine
and
glycine
to
produce
three
loops
that
are
essential
for
high
-affinity
binding
to
its
ligand
.
Nearly
all
reported
CADASIL
-associated
mutations
result
in
gain
or
loss
of
a
cysteine
residue
within
the
EGF
-like
domains
.
Only
a
few
cysteine-sparing
NOTCH
3
mutations
have
been
documented
in
the
patients
with
CADASIL
to
date
.
Here
,
we
reported
a
Chinese
CADASIL
family
with
a
cysteine-sparing
NOTCH
3
mutation
.
In
this
family
,
affected
patients
had
dizziness
,
memory
loss
,
gait
instability
,
or
hemiplegia
.
Brain
magnetic
resonance
imaging
(
MRI
)
showed
diffuse
leukoencephalopathy
with
confluent
signal
abnormalities
in
the
periventricular
white
matter
,
basal
ganglia
,
and
centrum
semiovale
bilaterally
.
By
screening
the
entire
coding
region
of
NOTCH
3
,
a
novel
missense
mutation
p
.
G
149
V
(
c
.
446
G
>
T
)
was
found
.
This
mutation
was
not
detected
in
400
normal
controls
.
Considering
the
critical
position
of
glycine
within
the
C-
loop
of
EGF
-like
domain
and
its
high
conservation
through
evolution
,
p
.
G
149
V
mutation
could
be
a
potential
pathogenic
cause
for
CADASIL
.