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[Holt-Oram syndrome: characterization of a novel mutation].
[holt-oram syndrome]
Cardiomyelic
syndromes
encompass
congenital
heart
disease
and
skeletal
malformations
of
the
upper
limbs
and
are
related
to
mutations
in
transcription
factors
with
T
-
Box
domains
.
Holt-
Oram
syndrome
is
caused
by
a
dominant
mutation
in
the
TBX
5
gene
that
alters
the
three
-dimensional
structure
of
the
protein
and
its
DNA
binding
function
.
Several
point
mutations
and
deletions
in
TBX
5
have
been
reported
in
patients
with
the
Holt-
Oram
syndrome
phenotype
.
The
proband
was
a
boy
with
a
large
atrial
septal
defect
ostium
secundum
type
and
a
ventricular
septal
defect
,
diagnosed
by
clinical
findings
(
heart
murmur
)
and
echocardiography
.
He
also
presented
slightly
hypoplastic
thumbs
with
distal
bilateral
placement
and
an
implantation
index
of
0
.
19
(
compared
with
an
average
of
0
.
50
for
his
gestational
age
at
birth
)
.
The
boy
was
referred
to
the
department
of
medical
genetics
to
rule
out
22
q
11
.
2
microdeletion
syndrome
.
Karyotype
and
fluorescence
in
situ
hybridization
at
locus
D
22
S
75
were
both
normal
.
Because
of
his
clinical
findings
,
molecular
study
for
Holt-
Oram
syndrome
was
indicated
,
leading
to
the
finding
of
a
mutation
at
intron
7
of
TBX
5
,
probably
producing
a
splicing
alteration
of
the
gene
and
resulting
in
a
protein
truncated
at
its
C-
terminal
end
.
The
proband
's
parents
presented
the
wild
type
sequence
of
the
gene
,
thus
indicating
that
the
mutation
was
produced
de
novo
,
although
a
possible
germinal
mosaicism
in
the
parents
could
not
be
ruled
out
.
Holt-
Oram
syndrome
is
the
most
frequent
cause
of
cardiomyelic
syndrome
.
All
children
with
heart
malformations
and
abnormalities
of
the
upper
limbs
such
as
absent
,
hypoplastic
,
distally
placed
or
triphalangic
thumbs
should
undergo
molecular
studies
for
this
syndrome
.