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Cohen syndrome is associated with major glycosylation defects.
[cohen syndrome]
Cohen
syndrome
(
CS
)
is
a
rare
autosomal
recessive
disorder
with
multisytemic
clinical
features
due
to
mutations
in
the
VPS
13
B
gene
,
which
has
recently
been
described
encoding
a
mandatory
membrane
protein
involved
in
Golgi
integrity
.
As
the
Golgi
complex
is
the
place
where
glycosylation
of
newly
synthesized
proteins
occurs
,
we
hypothesized
that
VPS
13
B
deficiency
,
responsible
of
Golgi
apparatus
disturbance
,
could
lead
to
glycosylation
defects
and
/
or
mysfunction
of
this
organelle
,
and
thus
be
a
cause
of
the
main
clinical
manifestations
of
CS
.
The
glycosylation
status
of
CS
serum
proteins
showed
a
very
unusual
pattern
of
glycosylation
characterized
by
a
significant
accumulation
of
agalactosylated
fucosylated
structures
as
well
as
asialylated
fucosylated
structures
demonstrating
a
major
defect
of
glycan
maturation
in
CS
.
However
,
CS
transferrin
and
α
1
-
AT
profiles
,
two
liver
-derived
proteins
,
were
normal
.
We
also
showed
that
intercellular
cell
adhesion
molecule
1
and
LAMP-
2
,
two
highly
glycosylated
cellular
proteins
,
presented
an
altered
migration
profile
on
SDS
-PAGE
in
peripheral
blood
mononuclear
cells
from
CS
patients
.
RNA
interference
against
VPS
13
B
confirmed
these
glycosylation
defects
.
Experiments
with
Brefeldin
A
demonstrated
that
intracellular
retrograde
cell
trafficking
was
normal
in
CS
fibroblasts
.
Furthermore
,
early
endosomes
were
almost
absent
in
these
cells
and
lysosomes
were
abnormally
enlarged
,
suggesting
a
crucial
role
of
VPS
13
B
in
endosomal-lysosomal
trafficking
.
Our
work
provides
evidence
that
CS
is
associated
to
a
tissue-
specific
major
defect
of
glycosylation
and
endosomal-lysosomal
trafficking
defect
,
suggesting
that
this
could
be
a
new
key
element
to
decipher
the
mechanisms
of
CS
physiopathology
.
Diseases
Validation
Diseases presenting
"liver-derived proteins"
symptom
cohen syndrome
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