β-Thalassemia: HBB Prenatal Test (Full Gene Sequencing)

Amniotic fluid or chorionic villus sample (CVS) or cultured amniocytes or cultured villi. Cultured cells are required for testing. Direct specimens can be submitted, but a culturing fee may be included. Maternal and paternal blood samples submitted on separate test request forms for 252827 (charges may apply). Maternal blood should also be ordered for Maternal Cell Contamination [511402], required for fetal testing.

10 to 15 mL amniotic fluid or 20 mg CVS or two T25 flasks cultured amniocytes or two T25 flasks cultured villi and 7 mL whole blood for parental samples.

10 mL amniotic fluid or 10 mg CVS. 3 mL whole blood for parental samples.

Sterile plastic conical tube or two confluent T-25 flasks for fetal testing; lavender top (EDTA) or yellow-top (ACD) tube for blood.

Use for prenatal analysis. Can confirm a clinical diagnosis of β-thalassemia, detect carriers, and help to establish a prognosis.

This method does not reliably detect mosaic variants; large deletions; large duplications, inversions, or other rearrangements; deep intronic variants; it may be affected by allele-dropout; it may not allow determination of the exact numbers of T/A or microsatellite repeats; and it does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies.

DNA sequencing

Normal equals reference sequence or variants that are known or predicted to be benign; abnormal equals all other variants.

β-thalassemia is a typically autosomal recessive form of severe anemia. Prevalence is estimated at 1:100,000 worldwide and at 1:10,000 in the European Union, reflecting the increased prevalence in Mediterranean populations. Based on disease severity, three of β-thalassemia are distinguished: β-thalassemia major (also known as Cooley's anemia), β-thalassemia intermedia, and β-thalassemia minor (also known as β-thalassemia minor is mostly asymptomatic but may be accompanied by mild anemia. In contrast, β-thalassemia major is characterized by infancy-onset severe anemia and requires life-long blood transfusions for survival. By definition, the intermediate form requires only intermittent blood transfusions for survival. Bone marrow or cord blood transplantation offers a cure, especially if performed before lasting organ damage has developed. Early diagnosis is therefore crucial, to allow timely treatment initiation. Distinction between the intermediate and major forms is also important, to avoid both unnecessary transfusions and unnecessary delay of required regular transfusions, which can increase the risk that the patient may develop multiple antibodies against donor red blood cells. Genetic testing can help with this diagnosis, since severity of β-thalassemia can partially be predicted from the nature of the causative mutations in HBB, the gene coding for β-globin. In addition, genetic testing can also identify mutations associated with rare cases of dominant inherited β-thalassemia. Once the mutations causing β-thalassemia in a specific family have been identified, genetic testing for these mutations can also help to diagnose affected siblings of patients prenatally or directly after birth and facilitate genetic counseling in other relatives.