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A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect.
[dentinogenesis imperfecta]
Mutations
in
the
DSPP
gene
have
been
identified
in
nonsyndromic
hereditary
dentin
defects
,
but
the
genotype-phenotype
correlations
are
not
fully
understood
.
Recently
,
it
has
been
demonstrated
that
the
mutations
of
DSPP
affecting
the
IPV
leader
sequence
result
in
mutant
DSPP
retention
in
rough
endoplasmic
reticulum
(
ER
)
.
In
this
study
,
we
identified
a
Korean
family
with
dentinogenesis
imperfecta
type
III
.
To
identify
the
disease
causing
mutation
in
this
family
,
we
performed
mutational
analysis
based
on
candidate
gene
sequencing
.
Exons
and
exon-intron
boundaries
of
DSPP
gene
were
sequenced
,
and
the
effects
of
the
identified
mutation
on
the
pre-m
RNA
splicing
and
protein
secretion
were
investigated
.
Candidate
gene
sequencing
revealed
a
mutation
(
c
.
50
C
>
T
,
p
.
P
17
L
)
in
exon
2
of
the
DSPP
gene
.
The
splicing
assay
showed
that
the
mutation
did
not
influence
pre-m
RNA
splicing
.
However
,
the
mutation
interfered
with
protein
secretion
and
resulted
in
the
mutant
protein
remaining
largely
in
the
ER
.
These
results
suggest
that
the
mutation
affects
ER-
to
-Golgi
apparatus
export
and
results
in
the
reduction
of
secreted
DSPP
and
ER
overload
.
This
may
induce
cell
stress
and
damage
processing
and
/
or
transport
of
dentin
matrix
proteins
or
other
critical
proteins
.