Detection and characterisation of β-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification
Detection and characterisation of β-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification
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DOI：
10.1136/jcp.2009.067538
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发表时间：
2009-12-01
影响因子：
3.4
通讯作者：
Chan, L. C.
中科院分区：
文献类型：
--
作者：
So, C. C.;So, A. C. Y.;Chan, L. C.
背景：导致地中海贫血症和遗传性胎儿血红蛋白残留(HPFH)的β-珠蛋白簇缺失并不常见，也很难检测到。目的：研究中国人β-珠蛋白簇缺失的频率和性质。方法：对106例疑似存在b-珠蛋白簇缺失的地中海贫血或HPFH患者进行研究。使用一种使用多重连接依赖的探针扩增(MLPA)的商用试剂盒来筛选缺失。结果：在17例患者中发现17个b-珠蛋白簇缺失：8个中国人((A)Gamma Delta beta)(0)地中海贫血，7个东南亚(越南)缺失和2个泰国((A)Gamma Delta Beta)(0)地中海贫血。在β地中海贫血症中检测到的唯一缺失类型是中国人((A)伽马β地中海贫血症)(0)地中海贫血症。HPFH缺失型仅见于1例泰国((A)Gamma Delta beta)(0)地中海贫血症。表现为β地中海贫血症特征和HbF升高的缺失均为东南亚(越南)缺失型。当这些缺失与典型的β-地中海贫血症突变在复合杂合态中共同遗传时，表型可能会非常不同。结论：在中国人群中，β-珠蛋白簇中只有相对较少的缺失类型。MLPA是一种快速有效的筛查这些缺失的方法。这些缺失的特征允许开发更简单和更特异的基于聚合酶链式反应的常规诊断检测方法。准确的表型预测并不总是可行的。许多HPFH病例的分子缺陷仍有待发现。
Background: Deletions in the beta-globin cluster causing thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) are uncommon and difficult to detect. Data in Chinese are very scarce.Aims: To use a recently available technique to investigate the frequencies and nature of beta-globin cluster deletions in Chinese.Methods: 106 subjects with phenotypes of thalassaemia or HPFH and suspected to have deletions in the b-globin cluster were studied. A commercially available kit employing multiplex ligation-dependent probe amplification (MLPA) was used to screen for deletions. Gap PCR and direct nucleotide sequencing were used to characterise deletions detected.Results: 17 deletions in the b-globin cluster were found in 17 patients: 8 of Chinese ((A)gamma delta beta)(0) thalassaemia, 7 of Southeast Asian (Vietnamese) deletion and 2 of Thai ((A)gamma delta beta)(0) thalassaemia. The only type of deletion detected in delta beta-thalassaemia was Chinese ((A)gamma delta beta)(0) thalassaemia. The deletional form of HPFH was rarely seen in only 1 case of Thai ((A)gamma delta beta)(0) thalassaemia. Deletions presenting as beta-thalassaemia trait and raised HbF were all of the Southeast Asian (Vietnamese) deletion type. When these deletions were co-inherited with classical beta-thalassaemia mutations in compound heterozygous states, the phenotypes could be very variable.Conclusions: In the Chinese population, there are only relatively few types of deletions seen in the beta-globin cluster. MLPA is a fast and effective way of screening for these deletions. Characterisation of these deletions allows the development of simpler and more specific PCR-based tests for routine diagnostic use. Accurate prediction of phenotype is not always feasible. The molecular defects in many cases of HPFH still await discovery.