Preferred test for molecular confirmation of beta thalassemia or a hemoglobinopathy involving the beta-globin gene.
- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 2 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Beta thalassemia is caused by decreased or absent synthesis of the hemoglobin beta-chain resulting in variable clinical presentations ranging from mild anemia to transfusion dependence. Structural hemoglobinopathies may result in sickling disorders, microcytic or hemolytic anemia, cyanosis, or erythrocytosis. Hereditary persistence of fetal hemoglobin (HPFH) is a clinically benign condition caused by variants within the beta globin gene cluster that alter normal hemoglobin switching and result in persistent fetal hemoglobin (Hb F) production.
Incidence: Varies by ethnicity.
Inheritance: Usually autosomal recessive, infrequently autosomal dominant.
Cause: Pathogenic variants within the HBB gene or variants involving the beta globin gene cluster and its regulatory elements.
Clinical Sensitivity: 99 percent for beta thalassemia and hemoglobinopathies associated with the HBB gene.
Methodology: Bidirectional sequencing of the HBB coding regions, intron-exon boundaries, proximal promoter, untranslated regions, and intronic variants IVS-II-654, IVS-II-705 and IVS-II-745. Multiplex ligation-dependent probe amplification (MLPA) of the beta globin gene cluster (HBB, HBD, HBG1, HBG2, HBE1) and its locus control region.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Breakpoints of large deletions will not be determined; therefore, the precise clinical phenotype associated with a particular deletion (e.g., HPFH vs. delta-beta thalassemia) may not be known. Intragenic deletions in the beta globin cluster genes, other than HBB, may not be detected. This assay does not assess for sequence variants within the coding or regulatory regions of HBD, HBG1, HBG2 or HBE1. Apparent copy number changes detected by probes solely in the HBG1-HBG2 region will not be reported, as they can result from benign sequence variants or gene conversion events.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2010118||Beta Globin (HBB) Seq, Del/Dup Spcm||31208-2|
|2010119||Beta Globin (HBB) Seq, DelDup Interp||21689-5|