Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease.
[krabbe disease]
The
characterization
of
the
underlying
GALC
gene
lesions
was
performed
in
30
unrelated
patients
affected
by
Krabbe
disease
,
an
autosomal
recessive
leukodystrophy
caused
by
the
deficiency
of
lysosomal
enzyme
galactocerebrosidase
.
The
GALC
mutational
spectrum
comprised
33
distinct
mutant
(
including
15
previously
unreported
)
alleles
.
With
the
exception
of
4
novel
missense
mutations
that
replaced
evolutionarily
highly
conserved
residues
(
p
.
P
318
R
,
p
.
G
323
R
,
p
.
I
384
T
,
p
.
Y
490
N
)
,
most
of
the
newly
described
lesions
altered
mRNA
processing
.
These
included
7
frameshift
mutations
(
c
.
61
delG
,
c
.
408
delA
,
c
.
521
delA
,
c
.
1171
_
1175
delCATTCinsA
,
c
.
1405
_
1407
delCTCinsT
,
c
.
302
_
308
dupAAATAGG
,
c
.
1819
_
1826
dupGTTACAGG
)
,
3
nonsense
mutations
(
p
.
R
69
X
,
p
.
K
88
X
,
p
.
R
127
X
)
one
of
which
(
p
.
K
88
X
)
mediated
the
skipping
of
exon
2
,
and
a
splicing
mutation
(
c
.
1489
+
1
G
>
A
)
which
induced
the
partial
skipping
of
exon
13
.
In
addition
,
6
previously
unreported
GALC
polymorphisms
were
identified
.
The
functional
significance
of
the
novel
GALC
missense
mutations
and
polymorphisms
was
investigated
using
the
MutPred
analysis
tool
.
This
study
,
reporting
one
of
the
largest
genotype-phenotype
analyses
of
the
GALC
gene
so
far
performed
in
a
European
Krabbe
disease
cohort
,
revealed
that
the
Italian
GALC
mutational
profile
differs
significantly
from
other
populations
of
European
origin
.
This
is
due
in
part
to
a
GALC
missense
substitution
(
p
.
G
553
R
)
that
occurs
at
high
frequency
on
a
common
founder
haplotype
background
in
patients
originating
from
the
Naples
region
.
Diseases
Validation
Diseases presenting
"newly described lesions"
symptom
krabbe disease
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom