Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Molecular basis for the Kallmann syndrome-linked fibroblast growth factor receptor mutation.
[kallmann syndrome]
Kallmann
syndrome
(
KS
)
is
a
developmental
disease
that
expresses
in
patients
as
hypogonadotropic
hypogonadism
and
anosmia
.
KS
is
commonly
associated
with
mutations
in
the
extracellular
D
2
domain
of
the
fibroblast
growth
factor
receptor
(
FGFR
)
.
In
this
study
,
for
the
first
time
,
the
molecular
basis
for
the
FGFR
associated
KS
mutation
(
A
168
S
)
is
elucidated
using
a
variety
of
biophysical
experiments
,
including
multidimensional
NMR
spectroscopy
.
Secondary
and
tertiary
structural
analysis
using
far
UV
circular
dichroism
,
fluorescence
and
limited
trypsin
digestion
assays
suggest
that
the
KS
mutation
induces
subtle
tertiary
structure
change
in
the
D
2
domain
of
FGFR
.
Results
of
isothermal
titration
calorimetry
experiments
show
the
KS
mutation
causes
a
10
-
fold
decrease
in
heparin
binding
affinity
and
also
a
complete
loss
in
ligand
(
FGF-
1
)
binding
.
(
1
)
H-
(
15
)
N
chemical
perturbation
data
suggest
that
complete
loss
in
the
ligand
(
FGF
)
binding
affinity
is
triggered
by
a
subtle
conformational
change
that
disrupts
crucial
structural
interactions
in
both
the
heparin
and
the
FGF
binding
sites
in
the
D
2
domain
of
FGFR
.
The
novel
findings
reported
in
this
study
are
expected
to
provide
valuable
clues
toward
a
complete
understanding
of
the
other
genetic
diseases
linked
to
mutations
in
the
FGFR
.
Diseases
Validation
Diseases presenting
"mutations in the extracellular d2 domain of the fibroblast growth factor receptor"
symptom
kallmann syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom