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 mutations result in elevated hemoglobin (Hb) A2 and usually have slightly elevated Hb F levels

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

Evaluating microcytic neonatal anemia

Evaluating unexplained long standing microcytosis in the setting of normal iron studies and negative alpha-thalassemia testing/normal Hb A2 percentages

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

Confirming homozygosity vs hemizygosity of mutations 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 hereditary persistence of fetal hemoglobin.

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

This test can be used to identify a variety of conditions (listed below) that involve large deletions of the beta-globin gene cluster. These mutations 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 mutation

-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 mutations 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

• Thalassemia/Hemoglobinopathy Patient Information
• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)

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