Ordering Recommendation

Preferred test for molecular confirmation of β thalassemia or a hemoglobinopathy involving the β-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
This test is New York DOH approved.
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: 1 week; Refrigerated: 1 month; Frozen: 6 months

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, 5'proximal promoter and untranslated region, 3'polyadenylation signal and intronic variants c. 93-21 (IVS-I-110), c.316-197 (IVS-II-654), c.316-146 (IVS-II-705), c.316-106 (IVS-II-745), and c.316-86_316-85 (IVS-II-765 L1). 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 (eg., 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 Category

Laboratory Developed Test (LDT)

Note

N/A

Hotline History
N/A
CPT Codes

81363; 81364

Components
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
* 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
Beta Globin (HBB) Sequencing and Deletion/Duplication