Alpha Thalassemia Panel

Summary and Pricing

Test Method

Bi-Directional Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification Assay
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
6090 HBA1 and HBA2 81479 81259,81269 $1470 Order Options and Pricing
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
6090HBA1 and HBA281479 81259, 81269 $1470 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

The great majority of MLPA assays are completed within 20 days.  The great majority of reflexive Sanger sequencing are completed within an additional 18 days.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Hemoglobin A, the main form of hemoglobin, is a polypeptide comprised of two alpha and two beta chains. Alpha chains are encoded through the HBA1 and HBA2 genes. Defects in these genes result in alpha thalassemia, which is a common hemoglobin disorder commonly found in African and Asian populations. Carrier frequencies are >1% due to a selective advantage of malaria resistance in these individuals. There are four clinical conditions ranging in severity from asymptomatic to hydrops fetalis: silent carrier, alpha thalassemia trait, hemoglobin H (HbH), and hemoglobin Bart hydrops fetalis (Hb Bart). Disease severity is correlated to the degree of impaired alpha chain production (Origa and Moi. 2016. PubMed ID: 20301608; Harteveld and Higgs. 2010. PubMed ID: 20507641).

The two main clinical forms of alpha thalassemia are Hb Bart and HbH. Hb Bart syndrome is a neonatal lethal disease characterized by pleural and pericardial effusions, severe hypochromic anemia, ascites, and generalized edema. HbH disease, also referred to as alpha thalassemia intermedia, is characterized by microcytic hypochromic anemia, splenomegaly, jaundice, and in some cases skeletal changes primarily affecting facial features. Onset for HbH ranges from first years of life to adulthood. HbH individuals may also develop gallstones, have iron overload, or acute hemolytic episodes during infections or in response to oxidant drugs. In more severe forms HbH individuals may require blood transfusions. Patients with alpha thalassemia trait may have mild anemia, but are largely symptomatic (Origa and moi. 2016. PubMed ID: 20301608; Harteveld and Higgs. 2010. PubMed ID: 20507641; Galanello and Cao. 2011. PubMed ID: 21381239).

Genetics

Two neighboring genes with high homology, HBA1 and HBA2, comprise the 4 alpha globin alleles. Classification of the different forms of alpha thalassemia is determined by the loss or inactivation of the alpha globin alleles.

Condition

Genotype

Silent Carrier

-α/αα

Alpha thalassemia trait

-α/-α or --/αα

Hemoglobin H

--/-α

Hemoglobin Bart Hydrops

--/--

Deletions in the HBA1 and HBA2 genes are found in over 90% of alpha thalassemia cases with seven founder mutations accounting for ~85% of all alpha thalassemia cases: -α3.7, -α4.2, -(α)20.5, --SEA, --MED, --FIL, and –THAI. The -α3.7 and -α4.2 deletions result in loss of a single alpha globin gene whereas the -(α)20.5, --SEA, --MED, --FIL, and -–THAI deletions encompass both HBA1 and HBA2 genes. Several other loss of function variants including splicing alterations, insertions/deletions, and nonsense changes have been reported in both the HBA1 and HBA2 genes. Patients with non-deletional forms of alpha thalassemia often present with more severe disease. The most common structural variant found in Asian populations is Hemoglobin Constant Spring (HbCS) which abolishes the canonical termination codon in the HBA2 gene, c.427T>C (p.*143Gln) (Origa and Moi. 2016. PubMed ID: 20301608; Harteveld and Higgs. 2010. PubMed ID: 20507641; Galanello and Cao. 2011. PubMed ID: 21381239).

Clinical Sensitivity - Sanger Sequencing and MLPA

The most common pathogenic variant involving one or a few nucleotides found in Asian populations is Hemoglobin Constant Spring (HbCS) which abolishes the canonical termination codon in the HBA2 gene, c.427T>C (p.*143Gln). Missense, nonsense, insertions/deletions, splice site alterations, poly adenylation and promotor substitutions in the have been reported in the HBA1 and HBA2 genes. These pathogenic variants account for ~10% of all alpha thalassemia cases (Origa and Moi. 2016 PubMed ID: 20301608; Harteveld and Higgs. 2010. PubMed ID: 20507641; Galanello and Cao. 2011. PubMed ID: 21381239).

The -α3.7, -α4.2, -(α)20.5, --SEA, --MED, --FIL, and –THAI deletions account for ~85% of all pathogenic variants detected in alpha thalassemia patients. Other full gene deletions encompassing the HBA1 and/or HBA2 genes are found in ~<5% of cases (Origa and Moi. 2016 PubMed ID: 20301608; Harteveld and Higgs. 2010. PubMed ID: 20507641).

Testing Strategy

This test involves bidirectional sequencing using genomic DNA of all coding exons of the HBA1 and HBA2 gene plus ~10 bp of flanking non-coding DNA on each side as well as 5’ and 3’ untranslated regions, and the polyadenylation sequences. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in patients and relatives of patients or to confirm research results.

Multiplex Ligation-Dependent Probe Amplification (MLPA) enables the detection of deletion and duplications of single and multiple exons within a given gene (Eijk-Van Os and Schouten. 2011. PubMed ID: 20938835). This test involves analysis only of the specific gene(s) of interest for each patient. The MLPA test is designed to have coverage for all exons for each targeted gene. It is a semi-quantitative technique to determine relative copy number using a multiplex PCR-based reaction. Only hybridized and ligated adjacent probe oligonucleotides of approximately 60 nucleotides in length are amplified using PCR and thus are specific for the sequence of interest. A stuffer sequence attached to the probe ensures a particular length for deciphering the probe target. Therefore, MLPA enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. For additional information please see www.mlpa.com.

Indications for Test

Patients with HbH present with anemia, splenomegaly, and mild jaundice. Laboratory findings include hypochromia (low mean corpuscular hemoglobin), microcytosis (low mean corpuscular volume) with detectable inclusion bodies, moderate reticulocytosis, decreased hemoglobin levels. Ideal candidates have HPLC or capillary electrophoresis indicating Hb patterns consistent with HbH or Hb Bart (Origa and Moi. 2016. PubMed ID: 20301608; Harteveld and Higgs. 2010. PubMed ID: 20507641).

Genes

Official Gene Symbol OMIM ID
HBA1 141800
HBA2 141850
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Alpha Thalassemia AR 604131
Hemoglobin H Disease AR 613978

Related Test

Name
PGxome®

Citations

  • Eijk-Van Os and Schouten. 2011. PubMed ID: 20938835
  • Galanello and Cao. 2011. PubMed ID: 21381239
  • Harteveld and Higgs. 2010. PubMed ID: 20507641
  • Origa and Moi. 2016. PubMed ID: 20301608

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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