Prenatal Diagnosis Center, Quanzhou Women's and Children's Hospital, Quanzhou, 362000, Fujian Province, People's Republic of China.
Yaneng BIOscience (Shenzhen) Co. Ltd., Shenzhen, 518000, Guangdong, People's Republic of China.
Sci Rep. 2024 Apr 30;14(1):9966. doi: 10.1038/s41598-024-60604-7.
Hemoglobin (Hb) Lepore is a rare deletional δβ-thalassemia caused by the fusion between delta-beta genes, and cannot be identified by traditional thaltassemia gene testing technology. The aim of this study was to conduct molecular diagnosis and clinical analysis of Hb Lepore in four unrelated Chinese families using third generation sequencing. Decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and an abnormal Hb band were observed in the probands of the four families. However, no common α and β-thalassemia variants were detected in the enrolled families using polymerase chain reaction-reverse dot blot hybridization based traditional thalassemia gene testing. Further third-generation sequencing revealed similar Hb Lepore-Boston-Washington variants in all the patients, which were resulted from partial coverage of the HBB and HBD globin genes, leading to the formation of a delta-beta fusion gene. Specific gap-PCR and Sanger sequencing confirmed that all the patients carried a similar Hb Lepore-Boston-Washington heterozygote. In addition, decreased levels of MCH and Hb A2 were observed in the proband's wife of family 2, an extremely rare variant of Hb Nanchang (GGT > AGT) (HBA2:c.46G > A) was identified by third-generation sequencing and further confirmed by Sanger sequencing. This present study was the first to report the similar Hb Lepore-Boston-Washington in Chinese population. By combining the utilization of Hb capillary electrophoresis and third-generation sequencing, the screening and diagnosis of Hb Lepore can be effectively enhanced.
血红蛋白 Lepore 是一种罕见的缺失型 δβ-地中海贫血，由 δ-β 基因融合引起，不能通过传统的地中海贫血基因检测技术识别。本研究旨在采用第三代测序技术对四个无关的中国家庭中的血红蛋白 Lepore 进行分子诊断和临床分析。四个家庭的先证者的平均红细胞体积（MCV）、平均红细胞血红蛋白（MCH）水平降低，并出现异常 Hb 带。然而，应用聚合酶链反应-反向斑点杂交的传统地中海贫血基因检测技术，在纳入的家庭中未检测到常见的α和β-地中海贫血变异。进一步的第三代测序揭示了所有患者中存在相似的血红蛋白 Lepore-Boston-Washington 变异，这是由于 HBB 和 HBD 珠蛋白基因的部分覆盖导致形成 delta-beta 融合基因。特异性缺口-PCR 和 Sanger 测序证实所有患者均携带相似的血红蛋白 Lepore-Boston-Washington 杂合子。此外，在家庭 2 的先证者的妻子中观察到 MCH 和 HbA2 水平降低，第三代测序鉴定出一种极其罕见的 HbNanchang（GGT>AGT）（HBA2:c.46G>A）变异，并通过 Sanger 测序进一步证实。本研究首次报道了中国人群中相似的血红蛋白 Lepore-Boston-Washington。通过结合血红蛋白毛细管电泳和第三代测序的应用，可以有效提高血红蛋白 Lepore 的筛查和诊断能力。
