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Characterization of two unique α-globin gene cluster deletions causing α-thalassemia in Israeli Arabs.
[alpha-thalassemia]
The
molecular
basis
of
α-thalassemia
(
α-thal
)
is
complex
.
The
use
of
multiplex
ligation-dependent
probe
amplification
(
MLPA
)
has
offered
the
possibility
of
identifying
more
gene
deletions
causing
α-thal
.
Our
objective
was
to
determine
the
molecular
basis
of
two
patients
with
Hb
H
(
β
4
)
disease
.
By
using
MLPA
in
combination
with
comparative
genomic
hybridization
(
CGH
)
we
identified
two
novel
α-globin
gene
cluster
deletions
:
a
30
 
kb
deletion
(
patient
1
)
we
refer
to
as
-
-
(
JAL
)
and
a
large
216
 
kb
deletion
(
patient
2
)
we
refer
to
as
-
-
(
LOD
)
.
Patient
1
was
a
compound
heterozygote
for
-
-
(
JAL
)
and
-
α
(
3
.
7
)
(
rightward
deletion
)
.
Twelve
family
members
of
patient
1
carrying
the
-
-
(
JAL
)
deletion
were
available
for
evaluation
:
five
with
-
-
(
JAL
)
/
-
α
(
3
.
7
)
,
four
with
-
-
(
JAL
)
/
α
(
Hph
I
)
α
and
three
with
-
-
(
JAL
)
/
αα
.
Their
clinical
picture
of
compound
heterozygosity
was
compatible
with
moderate
Hb
H
disease
.
In
patient
2
(
-
-
(
LOD
)
/
-
α
(
3
.
7
)
)
,
no
additional
symptoms
were
present
despite
the
heterozygous
deletion
of
seven
known
genes
,
three
non
coding
RNAs
(
ncRNAs
)
,
four
unknown
genes
and
two
pseudo
genes
.
Further
analysis
of
more
patients
with
α-thal
deletions
will
have
implications
for
genetic
counseling
and
appropriate
therapy
.
Diseases
Validation
Diseases presenting
"comparative genomic hybridization"
symptom
22q11.2 deletion syndrome
achondroplasia
alpha-thalassemia
aniridia
canavan disease
cowden syndrome
dedifferentiated liposarcoma
holt-oram syndrome
kallmann syndrome
krabbe disease
monosomy 21
well-differentiated liposarcoma
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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