Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Defective lipid remodeling of GPI anchors in peroxisomal disorders, Zellweger syndrome, and rhizomelic chondrodysplasia punctata.
[zellweger syndrome]
Many
cell
surface
proteins
in
mammalian
cells
are
anchored
to
the
plasma
membrane
via
glycosylphosphatidylinositol
(
GPI
)
.
The
predominant
form
of
mammalian
GPI
contains
1
-
alkyl-
2
-
acyl
phosphatidylinositol
(
PI
)
,
which
is
generated
by
lipid
remodeling
from
diacyl
PI
.
The
conversion
of
diacyl
PI
to
1
-
alkyl-
2
-
acyl
PI
occurs
in
the
ER
at
the
third
intermediate
in
the
GPI
biosynthetic
pathway
.
This
lipid
remodeling
requires
the
alkyl-phospholipid
biosynthetic
pathway
in
peroxisome
.
Indeed
,
cells
defective
in
dihydroxyacetone
phosphate
acyltransferase
(
DHAP-AT
)
or
alkyl-
DHAP
synthase
express
only
the
diacyl
form
of
GPI
-anchored
proteins
.
A
defect
in
the
alkyl-phospholipid
biosynthetic
pathway
causes
a
peroxisomal
disorder
,
rhizomelic
chondrodysplasia
punctata
(
RCDP
)
,
and
defective
biogenesis
of
peroxisomes
causes
Zellweger
syndrome
,
both
of
which
are
lethal
genetic
diseases
with
multiple
clinical
phenotypes
such
as
psychomotor
defects
,
mental
retardation
,
and
skeletal
abnormalities
.
Here
,
we
report
that
GPI
lipid
remodeling
is
defective
in
cells
from
patients
with
Zellweger
syndrome
having
mutations
in
the
peroxisomal
biogenesis
factors
PEX
5
,
PEX
16
,
and
PEX
19
and
in
cells
from
patients
with
RCDP
types
1
,
2
,
and
3
caused
by
mutations
in
PEX
7
,
DHAP-AT
,
and
alkyl-
DHAP
synthase
,
respectively
.
Absence
of
the
1
-
alkyl-
2
-
acyl
form
of
GPI
-anchored
proteins
might
account
for
some
of
the
complex
phenotypes
of
these
two
major
peroxisomal
disorders
.
Diseases
Validation
Diseases presenting
"lethal genetic diseases"
symptom
zellweger syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom