Test ID: WBDD    
Beta-Globin Cluster Locus, Deletion/Duplication, Varies

Determining the etiology of hereditary persistence of fetal hemoglobin (HPFH) or delta-beta thalassemia

Diagnosing less common causes of beta thalassemia; these large deletional beta thalassemia variants result in elevated hemoglobin (Hb) A2 and usually have slightly elevated HbF levels

Distinguishing homozygous Hb S disease from a compound heterozygous HbS/large beta-globin cluster deletion disorder (ie, HbS/beta zero thalassemia, Hb S/delta-beta zero thalassemia, HbS/HPFH, HbS/gamma-delta-beta thalassemia)

Diagnosing complex thalassemias where the beta-globin gene and one or more of the other genes in the beta-globin cluster have been deleted

Evaluating and classifying unexplained increased HbF percentages

Evaluating microcytic neonatal anemia

Evaluating unexplained long standing microcytosis in the setting of normal iron studies and negative alpha thalassemia testing/normal HbA2 percentages

Confirming gene fusion hemoglobin variants such as Hb Lepore and Hb P-Nilotic

Confirming homozygosity vs hemizygosity of variants in the beta-like genes (HBB, HBD, HBG1, HBG2)

This test is not useful for diagnosis or confirmation of alpha thalassemia, the most common beta thalassemias, or hemoglobin variants. It also does not detect nondeletional HPFH.

This test can be used to identify a variety of conditions (see Highlights) that involve large deletions of the beta-globin gene cluster. These alterations will not be detected by DNA sequencing of the beta-globin gene.

This test is recommended to identify a variety of conditions involving large deletions or duplications within the beta-globin gene cluster locus region including:

-Identifying large deletions causing increased hemoglobin (Hb) F levels such as hereditary persistence of fetal hemoglobin (HPFH), delta-beta thalassemias, and gamma-delta-beta thalassemia

-Identifying beta thalassemia conditions in cases where beta gene sequencing did not find a beta thalassemia variant

-Confirming gene fusion hemoglobin variants such as Hb Lepore and Hb P-Nilotic

-Investigating newborns with unexplained microcytic anemia that is suspected to be caused by epsilon-gamma-delta-beta thalassemia

-Confirming homozygosity vs hemizygosity of variants in the beta-like genes (HBB, HBD, HBG1, HBG2)

-Investigating individuals older than 12 months of age with unexplained microcytosis and normal hemoglobin electrophoresis for whom more common causes of microcytosis such as iron deficiency and alpha thalassemia have been excluded

A hemoglobin electrophoresis evaluation (HBEL1 / Hemoglobin Electrophoresis Evaluation, Blood) is always indicated prior to beta-globin cluster locus deletion and duplication testing as these conditions can be complex and protein data allows accurate classification of the patient phenotype.

• Informed Consent for Genetic Testing
• Metabolic Hematology Patient Information
• Informed Consent for Genetic Testing (Spanish)

Polymerase Chain Reaction (PCR) Analysis/Multiplex Ligation-Dependent Probe Amplification (MLPA)