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ASN540SER mutation is associated with a mild form of hypochondroplasia: a 7 years follow-up in an Italian boy.
[achondroplasia]
Skeletal
dysplasias
(
SKD
)
are
genetic
disorders
that
result
in
the
abnormal
development
of
part
or
all
of
the
skeleton
and
are
commonly
associated
with
short
stature
.
The
most
common
SKDs
that
typically
result
in
short
stature
include
achondroplasia
/
hypochondroplasia
(
HCH
)
both
caused
by
different
mutations
in
the
same
gene
.
HCH
diagnosis
is
based
on
the
clinical
appearance
during
development
and
conventional
X-
ray
findings
.
In
about
70
%
of
patients
,
missense
mutations
in
the
gene
coding
for
the
fibroblast
Growth
Factor
Receptor
3
(
FGFR
3
)
affects
the
amino
acid
at
position
540
,
mostly
resulting
in
the
amino
acid
exchange
N
540
K
.
Subjects
with
HCH
,
heterozygous
for
the
N
540
K
substitution
are
significantly
more
disproportionate
than
individuals
without
this
mutation
.
We
report
the
clinical
and
radiographic
features
of
an
Italian
family
with
HCH
with
an
unusual
N
540
S
mutation
,
inside
the
common
mutation
hot
spot
of
this
condition
.
This
is
the
first
case
reported
in
Italy
and
the
third
in
the
literature
.
During
a
7
-
years
-follow-up
,
the
boy
started
the
puberty
at
the
age
of
11
.
3
years
and
the
growth
spurt
was
observed
between
13
.
7
and
14
.
9
years
(
+
9
.
1
cm
.
)
.
During
pubertal
development
the
sitting
height
(
SDS
)
improved
from
-
1
.
5
to
-
0
.
6
and
the
subischial
leg
length
(
SDS
)
progressed
from
-
2
.
6
to
-
3
.
3
.
At
the
age
of
16
.
7
year
the
standing
height
was
157
.
6
cm
(
-
2
.
4
SDS
)
,
testicular
volume
was
15
ml
and
bone
age
16
.
5
year
.
The
present
study
and
the
other
two
cases
reported
in
the
literature
stress
the
important
role
of
the
asn
540
site
in
the
tyrosine
kinase
I
domain
in
the
pathogenesis
of
HCH
and
underline
the
importance
that
,
in
patients
with
HCH
who
do
not
have
the
common
N
540
K
mutation
,
sequence
analysis
of
the
tyrosine
kinase
I
domain
of
FGFR
3
should
be
performed
to
exclude
other
changes
in
that
region
.
Diseases
Validation
Diseases presenting
"first case"
symptom
achondroplasia
adrenal incidentaloma
allergic bronchopulmonary aspergillosis
alpha-thalassemia
aniridia
aromatase deficiency
canavan disease
carcinoma of the gallbladder
child syndrome
cholangiocarcinoma
classical phenylketonuria
coats disease
cohen syndrome
congenital toxoplasmosis
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dentin dysplasia
dracunculiasis
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
fabry disease
familial mediterranean fever
focal myositis
gm1 gangliosidosis
harlequin ichthyosis
hodgkin lymphoma, classical
homocystinuria without methylmalonic aciduria
junctional epidermolysis bullosa
kabuki syndrome
krabbe disease
lamellar ichthyosis
legionellosis
liposarcoma
locked-in syndrome
malignant atrophic papulosis
monosomy 21
neonatal adrenoleukodystrophy
oculocutaneous albinism
omenn syndrome
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
primary hyperoxaluria type 1
proteus syndrome
pyomyositis
systemic capillary leak syndrome
thoracic outlet syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
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