α-Thalassemia, DNA Analysis

Whole blood, amniotic fluid, chorionic villus sample (CVS) (Submission of maternal blood is required for fetal testing.)

7 mL whole blood, 10 mL amniotic fluid or 20 mg CVS

3 mL whole blood, 5 mL amniotic fluid or 10 mg CVS

Lavender-top (EDTA) tube, yellow-top (ACD) tube, sterile plastic conical tube, or two confluent T-25 flasks for fetal testing

This test is designed to detect copy-number changes in the α-globin gene cluster (deletions and duplications) of 28 different sequences in the HBA region. In addition, the assay detects the presence of the Constant Spring (Hb CS) mutation. Other point mutations, and variants in other genes, will not be detected by this assay. Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.

Results of this test are labeled for research purposes only by the assay's manufacturer. The performance characteristics of this assay have not been established by the manufacturer. The result should not be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically established diagnostic product or procedure. The performance characteristics were determined by LabCorp.

Polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA)

α-Thalassemia (OMIM 141800) is the most common inherited disorder of hemoglobin (Hb) synthesis in the world, with gene frequencies varying between 1% and 98% throughout the tropics and subtropics. α-Thalassemia can occur in all ethnic groups but is more common in those of Southeast Asian descent. The American College of Obstetricians and Gynecologists recommends hemoglobinopathy screening for those of African, Southeast Asian, and Mediterranean descent. More than 95% of recognized α-thalassemia involves deletion of one or both α-globin genes from chromosome 16p13.3.

DNA analysis of the α-globin region (HBA1/HBA2, OMIM 141800/141850, 16pter-16p13.3) is performed by targeting 28 different sequences using multiplex ligation-dependent probe amplification (MLPA). This methodology detects genomic deletions and duplications involving this locus, including the seven most common types of α-Thalassemia deletions (α-3.7, α-4.2, SEA, MED, THAI, FIL, and α-(20.5)), as well the Constant Spring point mutation. DNA analysis of the common α-globin gene deletions performed by multiplex polymerase chain reaction (PCR) followed by agarose gel electrophoresis may, on occasion, be used for confirmatory purposes.