Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
A homozygous NOTCH3 mutation p.R544C and a heterozygous TREX1 variant p.C99MfsX3 in a family with hereditary small vessel disease of the brain.
[cadasil]
Mutations
in
the
TREX
1
and
NOTCH
3
genes
cause
retinal
vasculopathy
with
cerebral
leukodystrophy
(
RVCL
)
and
cerebral
autosomal
dominant
arteriopathy
with
subcortical
infarcts
and
leukoencephalopathy
(
CADASIL
)
,
respectively
.
Both
are
hereditary
small
vessel
diseases
of
the
brain
(
HSVDB
)
.
We
performed
mutational
analyses
of
TREX
1
in
genomic
DNA
from
39
unrelated
patients
who
were
NOTCH
3
-
negative
in
genetic
testing
,
selected
out
of
72
unrelated
consecutive
patients
with
HSVDB
.
Only
one
patient
had
a
TREX
1
sequence
variation
,
a
heterozygous
TREX
1
c
.
294
dupA
,
putatively
resulting
in
a
truncated
protein
,
p
.
C
9
9
MfsX
3
.
The
medical
history
of
the
patient
's
family
was
scrutinized
,
which
revealed
that
heterozygous
TREX
1
p
.
C
9
9
MfsX
3
was
not
segregating
with
the
HSVDB
.
Re-examination
of
the
NOTCH
3
sequence
data
of
the
proband
led
to
the
identification
of
a
homozygous
NOTCH
3
c
.
1630
C
>
T
(
p
.
R
544
C
)
mutation
,
which
segregated
with
the
HSVDB
in
the
family
.
The
proband
had
a
slightly
more
severe
phenotype
in
comparison
with
her
heterozygous
p
.
R
544
C
sister
.
TREX
1
mutation
is
not
a
common
cause
of
HSVDB
.
TREX
1
p
.
C
9
9
MfsX
3
is
not
a
dominant
mutation
.
Homozygosity
of
the
NOTCH
3
p
.
R
544
C
has
a
modestly
deleterious
effect
on
the
CADASIL
phenotype
.
The
NOTCH
3
mutation
may
cause
CADASIL
through
a
gain-of-toxic
function
effect
,
which
can
be
modified
by
other
genetic
or
environmental
factors
and
results
in
the
phenotypic
variation
of
CADASIL
.
Diseases
Validation
Diseases presenting
"leukodystrophy"
symptom
achondroplasia
adrenomyeloneuropathy
alexander disease
cadasil
canavan disease
carcinoma of the gallbladder
classical phenylketonuria
coats disease
fabry disease
gm1 gangliosidosis
krabbe disease
neonatal adrenoleukodystrophy
phenylketonuria
pyruvate dehydrogenase deficiency
wiskott-aldrich syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
This symptom has already been validated