Identification of a Novel 16.8Kb Deletion of the α-Globin Gene Cluster by Third-Generation Sequencing

• Published in: Hemoglobin 2024-07, Vol.48 (4), p.1-249
• Main Authors: Jiang, Fan, Huang, Shuang, Liu, Tuoen, Wang, Jieyu, Zhou, Jianying, Zuo, Liandong, Li, Jian, Li, Ru, Liao, Can, Li, Dongzhi
• Format: Article
• Language: English
• ISSN: 0363-0269; 1532-432X; 1532-432X
• DOI: 10.1080/03630269.2024.2378078

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.