HBB Deletion/Duplication Analysis

β-Thalassemia is a typically autosomal-recessive form of severe anemia. Prevalence is estimated at 1:100,000 worldwide and at 1:10,000 in the European Union, reflecting the increased prevalence in Mediterranean populations. Based on disease severity, three types of β-thalassemia are distinguished: β-thalassemia major (also known as Cooley's anemia), β-thalassemia intermedia, and β-thalassemia minor (also known as β-thalassemia trait). β-Thalassemia minor is mostly asymptomatic, but may be accompanied by mild anemia. In contrast, β-thalassemia major is characterized by infancy-onset severe anemia and requires life-long blood transfusions for survival. By definition, the intermediate form requires only intermittent blood transfusions for survival. Bone marrow or cord blood transplantation offers a cure, especially if performed before lasting organ damage has developed. Early diagnosis is, therefore, crucial to allow timely treatment initiation. Distinction between the intermediate and major forms is also important to avoid both unnecessary transfusions and unnecessary delay of required regular transfusions, which can increase the risk that the patient may develop multiple antibodies against donor red blood cells. Genetic testing can help with this diagnosis, since severity of β-thalassemia can partially be predicted from the nature of the causative mutations in HBB, the gene coding for β-globin. In addition, genetic testing can also identify mutations associated with rare cases of dominantly inherited β-thalassemia. Once the mutations causing β-thalassemia in a specific family have been identified, genetic testing for these mutations can also help to diagnose affected siblings of patients prenatally or directly after birth and facilitate genetic counseling in other relatives.