β-Thalassemia: HBB (Full Gene Sequencing)

Confirm a clinical diagnosis of β-thalassemia; detect carriers; help to establish a prognosis

In cases in which a known mutation can be documented, the physician may prefer to order β-Thalassemia: HBB (Known Mutation) [252827]. For testing of a prenatal specimen, please order β-Thalassemia: HBB Prenatal Test (Full Gene Sequencing) [252867].

Test orders must include an attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. In the case of family tests (ie, known mutations), please submit the result report of the first patient tested in the family (the index case), if not performed at a LabCorp facility. Other family members are subsequently tested for the specific mutation found in the first patient tested. For prenatal testing, submission of a maternal blood sample is required for fetal testing.

This method does not reliably detect mosaic variants, deep intronic variants, large deletions, large duplications, inversions or other rearrangements. Assay results may be affected by the presence of homopolymer repeats or by allele-dropout due to sequence polymorphisms in primer binding sites. This assay does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

DNA sequencing

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.