Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center affiliated with Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Department of Laboratory Medicine, He Xian Memorial Hospital, Southern Medical University, Guangzhou, China.
Hemoglobin. 2024 Jul;48(4):244-249. doi: 10.1080/03630269.2024.2378078. Epub 2024 Jul 15.
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 - deletion carrier. The result of multiplex ligation-dependent probe amplification (MLPA) suggested the existence of - 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.
重型α 地中海贫血（α-TM）常导致胎儿 Bart's 水肿和母亲严重的产科并发症。对有生育受影响的α-TM 患儿风险的夫妇进行逐步筛查是有效的预防方法，但一些罕见的地中海贫血基因型无法被检测到。一位 32 岁男性 HbA2（2.4%）低且轻度贫血，因其妻子为 - 缺失携带者，故进行了实时 PCR 基于多色熔解曲线分析（MMCA）。多重连接依赖性探针扩增（MLPA）的结果表明该先证者存在 - 缺失。通过设计的 MLPA 探针与更长的 PCR 相结合，发现了一个新的α-珠蛋白基因簇缺失，通过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。鉴定出一个从 1,53,226 到 1,54,538（GRch38/hg38）的片段，提示存在同源重组事件。第三代测序在获取复杂结构变异的准确信息方面是准确和高效的。
