Test Catalog

Test ID: WBDDR    
Beta-Globin Cluster Locus Deletion/Duplication, Blood

Useful For Suggests clinical disorders or settings where the test may be helpful

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 1 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)

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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


This test may result as a reflex secondary to testing from several evaluations (HAEVP / Hemolytic Anemia Evaluation; HBELC / Hemoglobin Electrophoresis Cascade, Blood; MEVP / Methemoglobinemia Evaluation; REVE / Erythrocytosis Evaluation; THEVP / Thalassemia and Hemoglobinopathy Evaluation).

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Large deletions involving the beta-globin cluster locus on chromosome 11 manifest with widely variable clinical phenotypes. Up to 10% of beta-thalassemia cases (dependent on ethnicity) are caused by large deletions in the beta-globin cluster. Other thalassemias including delta-beta-thalassemia, gamma-delta-beta-thalassemia, and epsilon-gamma-delta-beta-thalassemia also result from functional loss of genes or the locus control region (LCR) that controls globin gene expression. In addition, hereditary persistence of fetal hemoglobin (HPFH) is caused by deletions of variable size along the beta globin cluster locus. Most, but not all, of the large deletion beta globin cluster disorders are associated with variably elevated hemoglobin (Hb) F percentages that persist after 2 years of age. In addition, most manifest in microcytosis. A notable exception is HPFH, which can have normal to minimal decreased mean corpuscular volume (MCV) values. The correct classification of these deletions is important as they confer variable predicted phenotypes and some are more protective than others when found in combination with a second beta globin mutation, such as Hb S or beta thalassemia. In addition, identification of these deletions can explain lifelong microcytosis in the setting of normal iron studies and negative alpha-thalassemia molecular results.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Only orderable as a reflex. For more information see:

-HAEVP / Hemolytic Anemia Evaluation

-HBELC / Hemoglobin Electrophoresis Cascade, Blood

-MEVP / Methemoglobinemia Evaluation

-REVE / Erythrocytosis Evaluation

-THEVP / Thalassemia and Hemoglobinopathy Evaluation


An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Nondeletional subtypes of beta-thalassemia or hereditary persistence of fetal hemoglobin (HPFH) are not detected by this assay.


Hemoglobin electrophoresis and sequencing analysis of the beta-globin gene will be performed prior to this test to exclude other diagnoses or to indicate the diagnostic utility of this testing platform.


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.


In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Hein MS, Oliveira JL, Swanson KC, et al: Large Deletions Involving the Beta Globin Gene Complex: Genotype-Phenotype Correlation of 119 cases. Blood 2015;126:3374

2. Kipp BR, Roellinger SE, Lundquist PA, et al: Development and clinical implementation of a combination deletion PCR and multiplex ligation-dependent probe amplification assay for detecting deletions involving the human alpha-globin gene cluster. J Mol Diagn 2011 Sep;13(5):549-557. doi: 10.1016/j.jmoldx.2011.04.001. Epub 2011 Jun 25

3. Rund D, Rachmilewitz E: Beta-thalassemia. N Engl J Med 2005;353:1135-1146

4. Nussbaum R, McInnes R, Willard H: Principles of Molecular Disease: Lessons from the Hemoglobinopathies. In Thompson and Thompson Genetics in Medicine. Seventh edition. Philadelphia, PA, Saunders Elsevier, 2007, pp 323-342

5. Wood WG: Hereditary persistence of fetal hemoglobin and delta beta thalassemia. In Disorders of Hemoglobin, First edition, Cambridge University Press, New York, NY, 2001, pp 356-388