Identification of a β-Globin Gene Mutation with the Genotype β-28(A > G), IVS-I-5(G > A)/βCD 71/72(+A) Using Third-Generation Sequencing

• Published in: Hemoglobin 2025-01, p.1-6
• Main Authors: Zeng, Guang-Kuan, Yang, Yan-Fang, Ge, Yi-Yuan, Yang, Ying, Lai, Bai-Ru, Cao, Yan-Bin, Yu, Xiao-Hua, Yang, Li-Ye
• Format: Article
• Language: English
• ISSN: 0363-0269; 1532-432X; 1532-432X
• DOI: 10.1080/03630269.2024.2446371

This study presents the hematological and genetic analysis of a child with severe β-thalassemia harboring triple heterozygous mutations. The child, diagnosed with anemia at the age of 1 year, became transfusion-dependent and maintained a hemoglobin level of 72.00-84.00 g/L following regular blood transfusions. At the age of 9 years, genetic analysis was conducted using PCR-reverse dot blot (PCR-RDB), Sanger sequencing, and third-generation nanopore sequencing. Sanger sequencing identified a triple heterozygous mutation in the β-globin gene: -28(A > G) ( :c.-78A > G), IVS-I-5(G > A) ( :c0.92 + 5G > A), and CD 71/72(+A) ( :c.216_217insA). Nanopore sequencing further confirmed the genotype as β /β . The combination of these mutations represents a rare β-thalassemia genotype in China, contributing to the β-globin gene mutation database for the Chinese population. This study highlights the importance of employing family analysis or third-generation sequencing technologies to clarify complex mutation linkages when Sanger sequencing alone cannot determine the relationship between multiple mutations.