Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome.
[cadasil]
Lateral
meningocele
syndrome
(
LMS
,
OMIM
%
130720
)
,
also
known
as
Lehman
syndrome
,
is
a
very
rare
skeletal
disorder
with
facial
anomalies
,
hypotonia
and
meningocele
-related
neurologic
dysfunction
.
The
characteristic
lateral
meningoceles
represent
the
severe
end
of
the
dural
ectasia
spectrum
and
are
typically
most
severe
in
the
lower
spine
.
Facial
features
of
LMS
include
hypertelorism
and
telecanthus
,
high
arched
eyebrows
,
ptosis
,
midfacial
hypoplasia
,
micrognathia
,
high
and
narrow
palate
,
low-set
ears
and
a
hypotonic
appearance
.
Hyperextensibility
,
hernias
and
scoliosis
reflect
a
connective
tissue
abnormality
,
and
aortic
dilation
,
a
high
-pitched
nasal
voice
,
wormian
bones
and
osteolysis
may
be
present
.
Lateral
meningocele
syndrome
has
phenotypic
overlap
with
Hajdu-
Cheney
syndrome
.
We
performed
exome
resequencing
in
five
unrelated
individuals
with
LMS
and
identified
heterozygous
truncating
NOTCH
3
mutations
.
In
an
additional
unrelated
individual
Sanger
sequencing
revealed
a
deleterious
variant
in
the
same
exon
33
.
In
total
,
five
novel
de
novo
NOTCH
3
mutations
were
identified
in
six
unrelated
patients
.
One
had
a
26
bp
deletion
(
c
.
6461
_
6486
del
,
p
.
G
2154
fsTer
78
)
,
two
carried
the
same
single
base
pair
insertion
(
c
.
6692
_
93
insC
,
p
.
P
2231
fsTer
11
)
,
and
three
individuals
had
a
nonsense
point
mutation
at
c
.
6247
A
>
T
(
pK
2083
*
)
,
c
.
6663
C
>
G
(
p
.
Y
2221
*
)
or
c
.
6732
C
>
A
,
(
p
.
Y
2244
*
)
.
All
mutations
cluster
into
the
last
coding
exon
,
resulting
in
premature
termination
of
the
protein
and
truncation
of
the
negative
regulatory
proline-glutamate-serine-threonine
rich
PEST
domain
.
Our
results
suggest
that
mutant
mRNA
products
escape
nonsense
mediated
decay
.
The
truncated
NOTCH
3
may
cause
gain-of-function
through
decreased
clearance
of
the
active
intracellular
product
,
resembling
NOTCH
2
mutations
in
the
clinically
related
Hajdu-
Cheney
syndrome
and
contrasting
the
NOTCH
3
missense
mutations
causing
CADASIL
.
©
2014
Wiley
Periodicals
,
Inc
.
Diseases
Validation
Diseases presenting
"scoliosis reflect a connective tissue abnormality"
symptom
cadasil
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom