Abstract：
α-thalassemia major (α-TM) often causes Hb Bart\'s (c4) hydrops fetalis and severe obstetric complications in the mother. Step-wise screening for couples at risk of having offspring(s) affected by α-TM is the efficient prevention method but some rare genotypes of thalassemia cannot be detected. A 32-year-old male with low HbA2 (2.4%) and mild anemia was performed real-time PCR-based multicolor melting curve analysis (MMCA) because his wife was -SEA deletion carrier. The result of multiplex ligation-dependent probe amplification (MLPA) suggested the existence of -SEA deletion in the proband. A novel deletion of the α-globin gene cluster was found using self-designed MLPA probes combined with longer PCR, which was further accurately described to be 16.8Kb (hg38, Chr16:1,65,236-1,82,113) deletion by the third-generation sequencing. A fragment ranging from 1,53,226 to 1,54,538(GRch38/hg38) was identified which suggested the existence of the homologous recombination event. The third-generation sequencing is accurate and efficient in obtaining accurate information for complex structural variations.
摘要：
重型α-地中海贫血(α-TM)常引起HbBart(c4)胎儿水肿和母亲严重的产科并发症。逐步筛查具有受α-TM影响的后代风险的夫妇是有效的预防方法，但无法检测到某些罕见的地中海贫血基因型。一名32岁的男性低HbA2（2.4％）和轻度贫血进行了基于实时PCR的多色熔解曲线分析（MMCA），因为他的妻子是-SEA缺失携带者。多重连接依赖性探针扩增（MLPA）的结果表明在先证中存在-SEA缺失。使用自行设计的MLPA探针结合较长的PCR发现了α-珠蛋白基因簇的新缺失，第三代测序进一步准确描述为16.8Kb(hg38,Chr16:1,65,236-1,82,113)缺失。鉴定了范围从1,53,226至1,54,538(GRch38/hg38)的片段,其表明同源重组事件的存在。第三代测序在获得复杂结构变异的准确信息方面是准确和有效的。
