Abstract：
Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs. In this study, two novel CNVs, a tandem duplication (αααα159) and deletion (--259), were identified in two Chinese families with thalassemia patients, according to the results of hematologic analysis, routine genetic testing for thalassemia, multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and other molecular methods. Co-inherited with βCD41-42 mutation and --SEA deletion separately, αααα159 and --259 resulted in a patient with β-thalassemia intermedia and a lethal fetus with Hb Bart\'s hydrops fetalis syndrome, respectively. Next, a literature review was performed to summarize all known CNVs involving the α-globin gene cluster. The molecular structure characteristics of these CNVs were analyzed and the possible mechanism was explored. It is the first time to analyze the generation mechanism of genome arrangements in the α-globin gene cluster systematically.
摘要：
地中海贫血是世界范围内最常见的单基因疾病之一。地中海贫血的一个重要遗传原因是α-珠蛋白基因簇中的拷贝数变异(CNV)。然而,对这些CNV的详细信息和机制没有统一的总结和讨论。在这项研究中,两个新的CNVs，串联复制（αααα159）和缺失（-259），在两个患有地中海贫血的中国家庭中发现，根据血液学分析结果,地中海贫血的常规基因检测，多重连接依赖性探针扩增（MLPA），下一代测序（NGS）和其他分子方法。与βCD41-42突变和--SEA缺失同时遗传，ααα159和-259导致一名中间β-地中海贫血患者和一名患有HbBart胎儿水肿综合征的致死胎儿，分别。接下来,进行了文献综述，以总结所有已知的涉及α-珠蛋白基因簇的CNV。分析了这些CNV的分子结构特征，并探讨了可能的机理。首次系统地分析α-珠蛋白基因簇中基因组排列的产生机制。
