Application of third-generation sequencing technology in the genetic testing of thalassemia

Thalassemia is an autosomal recessive genetic disorder and a common form of Hemoglobinopathy. It is classified into alpha-thalassemia and beta-thalassemia. This disease is mainly prevalent in tropical and subtropical regions, including southern China. Severe alpha-thalassemia and intermediate alpha-thalassemia are among the most common birth defects in southern China. Intermediate alpha-thalassemia, also known as Hb H disease, is characterized by moderate anemia. Severe alpha-thalassemia, also known as Hb Bart's Hydrops fetalis syndrome, is a fatal condition. Infants with severe beta-thalassemia do not show symptoms at birth but develop severe anemia later, requiring expensive treatment. Most untreated patients with severe beta-thalassemia die in early childhood. Screening for thalassemia carriers and genetic diagnosis in high-prevalence areas significantly reduce the incidence of severe thalassemia. This review aims to summarize the genetic diagnostic approaches for thalassemia. Conventional genetic testing methods can identify 95-98% of thalassemia carriers but may miss rare thalassemia genotypes. Third-Generation Sequencing offers significant advantages in complementing other genetic diagnostic approaches, providing a basis for genetic counseling and prenatal diagnosis.