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Molecular characteristic of alpha thalassaemia among patients diagnosed in UKM Medical Centre.
[alpha-thalassemia]
Alpha
(
Α
)
thalassaemia
is
the
most
common
inherited
disorder
in
Malaysia
.
The
clinical
severity
is
dependant
on
the
number
of
Α
genes
involved
.
Full
blood
count
(
FBC
)
and
haemoglobin
(
Hb
)
analysis
using
either
gel
electrophoresis
,
high
performance
liquid
chromatography
(
HPLC
)
or
capillary
zone
electrophoresis
(
CE
)
are
unable
to
detect
definitively
alpha
thalassaemia
carriers
.
Definitive
diagnosis
of
Α-
thalassaemias
requires
molecular
analysis
and
methods
of
detecting
both
common
deletional
and
non-deletional
molecular
abnormailities
are
easily
performed
in
any
laboratory
involved
in
molecular
diagnostics
.
We
carried
out
a
retrospective
analysis
of
1623
cases
referred
to
our
laboratory
in
Universiti
Kebangsaan
Malaysia
Medical
Centre
(
UKMMC
)
for
the
diagnosis
of
Α-
thalassaemia
during
the
period
October
2001
to
December
2012
.
We
examined
the
frequency
of
different
types
of
alpha
gene
abnormalities
and
their
haematologic
features
.
Molecular
diagnosis
was
made
using
a
combination
of
multiplex
polymerase
reaction
(
PCR
)
and
real
time
PCR
to
detect
deletional
and
non-deletional
alpha
genes
relevant
to
southeast
Asian
population
.
Genetic
analysis
confirmed
the
diagnosis
of
Α-
thalassaemias
in
736
cases
.
Majority
of
the
cases
were
Chinese
(
53
.
1
%
)
followed
by
Malays
(
44
.
2
%
)
,
and
Indians
(
2
.
7
%
)
.
The
most
common
gene
abnormality
was
ΑΑ
/
-
-
(
SEA
)
(
64
.
0
%
)
followed
by
ΑΑ
/
-
Α
(
3
.
7
)
(
19
.
8
%
)
,
-
Α
(
3
.
7
)
/
-
-
(
SEA
)
(
6
.
9
%
)
,
ΑΑ
/
ΑΑCS
(
3
.
0
%
)
,
-
-
(
SEA
)
/
-
-
(
SEA
)
(
1
.
2
%
)
,
-
Α
(
3
.
7
)
/
-
Α
(
3
.
7
)
(
1
.
1
%
)
,
ΑΑ
/
-
Α
(
4
.
2
)
(
0
.
7
%
)
,
-
Α
(
4
.
2
)
/
-
-
(
SEA
(
0
.
7
%
)
,
-
Α
(
3
.
7
)
/
-
Α
(
4
.
2
)
(
0
.
5
%
)
,
ΑΑ
(
CS
)
/
-
-
SEA
)
(
0
.
4
%
)
,
ΑΑ
(
CS
)
/
ΑΑ
(
Cd
59
)
(
0
.
4
%
)
,
ΑΑ
(
CS
)
/
ΑΑ
(
CS
)
(
0
.
4
%
)
,
-
Α
(
3
.
7
)
/
ΑΑ
(
Cd
59
)
(
0
.
3
%
)
,
ΑΑ
/
ΑΑ
(
Cd
59
)
(
0
.
1
%
)
,
ΑΑ
(
Cd
59
)
/
ΑΑ
(
IVS
I
-
1
)
(
0
.
1
%
)
,
-
Α
(
3
.
7
)
/
ΑΑ
(
CS
)
(
0
.
1
%
)
and
-
-
(
SEA
)
/
ΑΑ
(
Cd
59
)
(
0
.
1
%
)
.
This
data
indicates
that
the
molecular
abnormalities
of
Α-
thalassaemia
in
the
Malaysian
population
is
heterogenous
.
Although
Α-
gene
deletion
is
the
most
common
cause
,
non-deletional
Α-
gene
abnormalities
are
not
uncommon
and
at
least
3
different
mutations
exist
.
Establishment
of
rapid
and
easy
molecular
techniques
is
important
for
definitive
diagnosis
of
alpha
thalassaemia
,
an
important
prerequisite
for
genetic
counselling
to
prevent
its
deleterious
complications
.
Diseases
Validation
Diseases presenting
"common deletional"
symptom
alpha-thalassemia
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