Molecular characteristic of alpha thalassaemia among patients diagnosed in UKM Medical Centre
- Author:
Raja Zahratul AZMA
;
AINOON Othman
;
HAFIZA Alauddin
;
AZLIN Ithnin
;
Noor FARISAH Abdul Razak
;
Nor HIDAYATI Sardi
;
Noor HAMIDAH Hussin
- Publication Type:Journal Article
- Keywords:
Deletional α-thalassaemia;
α-thalassaemia variant;
molecular analysis;
genetic polymorphism;
Malaysian population
- MeSH:
Thalassemia;
Patients
- From:The Malaysian Journal of Pathology
2014;36(1):27-32
- CountryMalaysia
- Language:English
-
Abstract:
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/-α3.7 (19.8%), -α3.7 /--SEA (6.9%), αα/ααCS (3.0%),
--SEA/--SEA (1.2%), -α3.7/-α3.7 (1.1%), αα/-α4.2 (0.7%), -α4.2/--SEA (0.7%), -α3.7/-α4.2 (0.5%), ααCS/--
SEA (0.4%), ααCS/ααCd59 (0.4%), ααCS/ααCS (0.4%), -α3.7/ααCd59 (0.3%), αα/ααCd59 (0.1%), αα Cd59/
ααIVS I-1 (0.1%), -α3.7/ααCS (0.1%) and --SEA /ααCd59 (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.
- Full text:P020141217533859993590.pdf
