Beta Thalassemia Globin Sequencing Gene Testing Blood

Beta globin gene sequencing is useful in the evaluation of beta globin chain variants and beta thalassemia. It detects almost all beta globin variants and the most common beta thalassemia mutations, although prevalence is ethnicity-dependent. Because these conditions are often complex, this test should always be interpreted in the context of protein studies, such as hemoglobin electrophoresis and RBC indices. The majority of beta globin chain variants are clinically and hematologically benign; however, some have important clinical consequences, such as erythrocytosis, cyanosis/hypoxia, chronic hemolysis, or unexplained microcytosis. Most of the common clinically significant hemoglobin (Hb) variants (ie, Hb S, Hb C, Hb E, and others) are easily distinguished by hemoglobin electrophoresis and do not require molecular analysis. In addition, they are frequently found in complex hemoglobin disorders due to multiple mutations, and accurate classification requires sequencing data within the context of protein data. In some instances, beta globin sequencing is necessary to identify or confirm the identity of rare variants, especially those associated with erythrocytosis and chronic hemolytic anemia. Rare hyperunstable variants (also termed dominant beta thalassemia mutations) result in hemolytic anemia and do not create protein stable enough to be detectable by protein methods, including stability studies. They are not always associated with elevated Hb A2 or microcytosis and, therefore, can be electrophoretically silent. These require a high degree of clinical suspicion as all electrophoretic testing as well as stability studies cannot exclude this condition. Beta thalassemia is an autosomal recessive condition characterized by decreased or absent synthesis of beta globin chains due to mutations in the beta globin gene (HBB). No abnormal protein is present and diagnosis by electrophoresis relies on hemoglobin fraction percentage alterations (ie, Hb A2 or Hb F elevations).