Azma Raja Zahratul, Ainoon Othman, Hafiza Alauddin, Azlin Ithnin, Noor Farisah Abudul Razak, Nor Hidayati Sardi, Noor Hamidah Hussin
Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Department of Pathology, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Kuala Lumpur, Malaysia.
Malays J Pathol. 2014 Apr;36(1):27-32.
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(Cd59) (0.4%), ΑΑ(CS)/ΑΑ(CS) (0.4%), -Α(3.7)/ΑΑ(Cd59) (0.3%), ΑΑ/ΑΑ(Cd59) (0.1%), ΑΑ(Cd59)/ ΑΑ(IVS I-1) (0.1%), -Α(3.7)/ΑΑ(CS) (0.1%) and --(SEA) /ΑΑ(Cd59) (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.
α地中海贫血是马来西亚最常见的遗传性疾病。临床严重程度取决于受累α基因的数量。全血细胞计数（FBC）和使用凝胶电泳、高效液相色谱（HPLC）或毛细管区带电泳（CE）的血红蛋白（Hb）分析无法明确检测出α地中海贫血携带者。α地中海贫血的确切诊断需要分子分析, 并且在任何从事分子诊断的实验室中都能轻松进行检测常见缺失和非缺失分子异常的方法。我们对2001年10月至2012年12月期间转诊至马来西亚国民大学医学中心（UKMMC）我们实验室进行α地中海贫血诊断的1623例病例进行了回顾性分析。我们检查了不同类型α基因异常的频率及其血液学特征。使用多重聚合酶反应（PCR）和实时PCR组合进行分子诊断，以检测与东南亚人群相关的缺失和非缺失α基因。基因分析确诊了736例α地中海贫血病例。大多数病例是华人（53.1%），其次是马来人（44.2%）和印度人（2.7%）。最常见的基因异常是αα/--(SEA)（64.0%），其次是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(Cd59)（0.4%）、αα(CS)/αα(CS)（0.4%）、-α(3.7)/αα(Cd59)（0.3%）、αα/αα(Cd59)（0.1%）、αα(Cd59)/αα(IVS I-1)（0.1%）、-α(3.7)/αα(CS)（0.1%）和--(SEA)/αα(Cd59)（0.1%）。该数据表明马来西亚人群中α地中海贫血的分子异常是异质性的。虽然α基因缺失是最常见的原因，但非缺失性α基因异常并不罕见，并且至少存在3种不同的突变。建立快速简便的分子技术对于α地中海贫血的确切诊断很重要，这是进行遗传咨询以预防其有害并发症的重要前提。
