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Beta Globin (HBB) Sequencing and Deletion/Duplication
2010117
Ordering Recommendation

Preferred test for molecular confirmation of beta thalassemia or a hemoglobinopathy involving the beta-globin gene.

Mnemonic
BG FGA
Methodology
Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification
Performed
Varies
Reported
28-35 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory, if possible.
ARUP Consult®
Disease Topics
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B). 
Specimen Preparation
Transport 3 mL whole blood. (Min: 2 mL) 
Storage/Transport Temperature
Refrigerated. 
Unacceptable Conditions
N/A 
Remarks
N/A 
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable 
Reference Interval
By report
Interpretive Data
Background Information: Beta Globin (HBB) Sequencing and Deletion/Duplication
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.

Compliance Statement C: The performance characteristics of this test were validated by ARUP Laboratories. The U.S. Food and Drug Administration (FDA) has not approved or cleared this test. However, FDA approval or clearance is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. ARUP is authorized under Clinical Laboratory Improvement Amendments (CLIA) and by all states to perform high-complexity testing. Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
N/A
CPT Code(s)
81403; 81404
Components
Component Test Code*Component Chart NameLOINC
2010118Beta Globin (HBB) Seq, Del/Dup Spcm21689-5
2010119Beta Globin (HBB) Seq, DelDup Interp31208-2
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases