Thalassemia, anautosomal recessive disorderis one of the most common genetic haematological disorders in the world. It is categorised intoalpha and beta thalassemia.
Alpha-thalassemia is caused by the deletion of alpha-globin genes in chromosome 16 contributing to the inadequate synthesis of alpha-globin peptide chains. The α-thalassemia involve the genes HBA1 and HBA2.
Beta Thalassemiais a hereditary blood disordercharacterized by point mutations or, deletions in thebeta globin gene on chromosome 11, resulting in reduction (b+) orabsence (b0) in beta chains of haemoglobin.Beta thalassemia is due to mutations in the HBB gene.
Reduction in the synthesis of beta globin results in the defective haemoglobin formation leads to anaemia. Beta thalassemia may be
- Major (βo/βo genotype) which is the most severe form where formation of functional β chains is completely absent, and therefore absence of haemoglobin A development.
- Intermediate (β+/βo or β+/β+ genotype), which is less severe type, where some haemoglobin A is produced.
- Minor (β/βo or β/β+ genotype)where mutation is present in only one of the two β globin alleles, thereby continuing the process of β chain production. Patients with Beta- thalassemia minor may be asymptomatic.
A genetic consultation is important for an accurate diagnosis, calculation of recurrence risk andprenatal testing.
Beta-thalassemia can be diagnosed using
1. Haematological testing
- Measurement of RBCs
- Peripheral Blood Smear
2. Molecular genetic testing
Targeted mutation analysis where prevalent molecular defects can be detected using ARMS PCR, real-time PCR or microarray technology.
Rare mutation detection where uncommon mutations can be identified using PCR followed by sequencing and sequence analysis in the HBB coding region and associated flanking regions with 99% sensitivity.
Some of the common mutations found in Indian population are as follows (Arora et al., 2001; Saxena et al., 1998):
- 619bp del (g.63201_63819del619)
- IVS1-5G>C (c.92+5G>C)
- IVS1-1G >T (c.92+1G>T)
- Fr41-42 (c.124_127delTTCTI)
- Fr8-9 (c.27_28insG)
Rare mutations identified in Indian population include:
Arora, S., Kabra, M., Maheshwari, M., Shastri, S., Kaur, D., Deka, D., Kriplani, A., Menon, P.S., 2001. Prenatal diagnosis of haemoglobinopathies. Natl Med J India 14, 340–342.
Saxena, R., Jain, P.K., Thomas, E., Verma, I.C., 1998. Prenatal diagnosis of β-thalassaemia: experience in a developing country. Prenatal Diagnosis 18, 1–7. https://doi.org/10.1002/(SICI)1097-0223(199801)18:1<1::AID-PD209>3.0.CO;2-Y