Fast-track strategy for the prevention of Hb Bart’s hydrops fetalis syndrome

Abstract

We propose a fast-track strategy [direct blood DNA analysis using a quantitative real-time polymerase chain reaction (PCR) technique] for the early risk detection and prenatal diagnosis of α(0)-thalassemia (SEA and Thai deletion). Blood DNA samples were obtained from a volunteer group of 1235 ANC couples. They were assessed using quantitative real-time PCR to detect carriers of α(0)-thalassemia (SEA and Thai deletion). At-risk couples were identified, and further prenatal diagnosis by amniocentesis was implemented. Fetal DNA was isolated from the amniotic cells and characterized by quantitative real-time PCR to detect the α(0)-thalassemia mutation, which was reconfirmed using the droplet digital PCR method. Fifteen at-risk couples were identified. The timing of prenatal diagnosis was appropriate for all couples and four of the fetuses were diagnosed with Bart’s hydrops fetalis. The results were compatible with those calculated using the Hardy-Weinberg equation for a recessively inherited single gene disorder. The conclusion was that the fast-track strategy could shorten screening policy timelines, promoting early risk detection for couples and early prenatal diagnosis. The fast-track strategy might be beneficial for the prevention of hemoglobin Bart’s hydrops fetalis syndrome. 针对 α(0) 地中海贫血（东南亚和泰国类型的贫血）的早期风险检测和产前诊断，我们提出了一种快速跟踪方法：使用定量实时聚合酶链反应 (PCR)，进行直接血液 DNA 分析。血液 DNA 样本取自 1,235 对 ANC 夫妇的志愿者组。使用定量实时 PCR 对其进行评估，以检测 α(0) 地中海贫血（东南亚和泰国类型的贫血）的载体。确定危险群夫妇之后，实施羊膜穿刺术，进行进一步的产前诊断。从羊膜细胞中分离出胎儿 DNA，使用定量实时 PCR 进行特征标度，以检测 α(0) 地中海贫血突变，然后使用液滴数字 PCR 法再次确认。共确定出十五对危险群夫妇。产前诊断这一时机适用于所有夫妇，其中四例胎儿确诊为巴特水肿胎儿。我们使用 Hardy-Weinberg 方程式来计算隐性遗传单基因疾病，结果一致。结论是，此快速跟踪方法可以缩短筛选策略时间表、方便夫妇进行早期风险检测、便于早期产前诊断。此快速跟踪方法或有利于预防血红蛋白巴特水肿胎儿综合征。

Keywords

• Fast-track diagnosis
• α(0)-thalassemia (SEA and Thai deletion) carriers
• prevention of Hb Bart’s hydrops fetalis syndrome.