Detection of complex hemoglobinopathies: recommendations on screening and DNA testing

  • E. Baysal | FRCP (London), Consultant Molecular Geneticist Head of Molecular Genetics, Senior Lecturer Dubai Genetic & Thalassemia Center, Dubai Health Authority, UAE, United Kingdom.


The following recommendations should be taken into account during the evaluation and elucidation of the complex hemoglobinopathies: a) in complex hemoglobinopathies performing DNA studies on all family members might be essential; b) complex gene-gene interactions offer major diagnostic challenges both at the technical and clinical level; c) hematological & DNA analyses must be run in parallel. Some cases may be straight forward but others may require indepth DNA work-up; d) co-inheritance of a-thalassemia offers added challenge as it may affect phenotype significantly; e) sickle cell anemia (SS), co-inherited with a-thal, can be a phenocopy of Sβ0-thal. The HbA2 increase can be mistaken for Sβ-thal. DNA Sequencing is imperative; f) only a selected number of normal MCV, MCH, borderline HbA2 cases must be referred for DNA analysis. However, in certain cases, following hematological and family evaluation, the β and d genes may need to be sequenced; g) DNA Sequencing will increasingly become the method of choice for screening and DNA mutation analysis. However, new methods like MLPA-which analyzes gene dosage- must be used more commonly to rule out deletion mutants to avoid false negative sequencing results; h) these recommendations should be reviewed every 2-3 years reflecting new methods, new findings and new findings from ethnic groups.


诊断和说明复杂血红蛋白病时,建议考虑以下几点: a)针对复杂的血红蛋白病,有必要对所有家庭成员开展DNA研究;b) 复杂的基因-基因交互作用可能使诊断在技术和临床层面上颇受挑战;c) 血液和DNA分析须同时进行。 有些病例简单,但另外一些病例可能需要开展深层次的DNA检查;d) 由于α型地中海贫血可能严重影响表型,α型地中海贫血的共同继承特征更具挑战;e) 共同继承α型地中海贫血的镰状细胞贫血(SS),可以作为Sβ0型地中海贫血的显型。 HbA2增量可能错误判断为Sβ0型地中海贫血。 必须进行DNA测序。f) 为方便DNA分析,必须参考选定数量的MCV、MCH、边境线HbA2正常病例。 然而,在某些情况下,继血液和家庭成员诊断后,可能需要测定β和δ基因的顺序;g) DNA测序将逐渐成为筛查和DNA突变分析的选择方法。 然而,为避免“假阴性”测序结果,必须更普遍地使用分析基因量的新方法(比如MLPA),以排除缺失突变体;h)应每2-3年审查一次这些推荐方法,反映新方法,新发现以及来自少数族群的新发现。



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haemoglobinopathies, screening.
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How to Cite
Baysal, E. (2011). Detection of complex hemoglobinopathies: recommendations on screening and DNA testing. Thalassemia Reports, 1(1), e31.