目的 探讨罕见α-地中海贫血的新生儿筛查与诊断。方法 应用全自动毛细管电泳技术对6 525例新生儿脐血进行血红蛋白定量分析，有Hb Bart’s区带的样本进行常规基因诊断（gap-PCR和PCR-RDB），对于未检出异常的样本，用多重PCR技术检测4种罕见α-基因缺失(--THAI, --FIL, --MED, - (α)20.5)，用PCR 产物直接测序法检测罕见非缺失型α-地贫。结果 6525例新生儿脐血样本中，检出Hb Bart’s阳性样本377例，其中基因确诊375例：包括14种基因型、383 个α-地贫等位基因；发现罕见α-地贫7例，包括2例--THAI /αα及5例罕见非缺失型α-地贫；发现1例α2-基因突变至与Hb Bart’s区带峰同区域的异常血红蛋白（Hb J-Wenchang-Wuming）。结论 毛细管电泳技术定量分析血红蛋白，准确、高效，应作为α-地贫高发地区的新生儿疾病筛查常规项目；在α-地贫高发地区应注意罕见α-地贫的筛查与诊断，防止漏诊导致重型地贫儿出生。
Objective To explore the methods and significance for neonatal screening and diagnosis about rare α-thalassemia. Method Automatic capillary electrophoresis (CE) was used to determinate Hb Bart’s amount in cord blood of 6,525 newborns. Samples with the presence of Hb Bart’s were confirmed by routine molecular analysis (gap-PCR and PCR-RDB). For samples of unknown genotype after gap-PCR and PCR-RDB, use a Multiplex PCR to detect four kinds of deletional α-thalassemia (--THAI, --FIL, --MED, - (α)20.5), then do gene sequencing for the whole α1-globin gene and α2-globin gene. Results Hb Bart’s, and 375 samples were confirmed by DNA testing, including 14 genotypes with 383 α–thalassemia alleles. 7 rare α-thalassemia genes were detected, including 2 --THAI /αα and 5 rare nondeletion type of α-thalassemia. At the same time, 1 sample with Hb J-Wenchang-Wuming, witch was appear at the same position with Hb Bart’s, was detected. Conclusions To screen for α-thalassemia, CE was proved to be an effective and accurate method. To prevent birth defects about hydrops fetalis or babies with transfusion-dependent α-thalassemia, rare α-thalassemia genotypes should be taken for suspected cases in high prevalence areas.
