Genetic Services >> GeneticSure | Screening >> ThalSure | HBB

ThalSure | HBB

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Condition Description Indications
Detection Specimen Requirement

 

Condition Description

Thalassemia is an autosomal recessive condition which mainly occurs due to abnormal formation of hemoglobin which results in improper oxygen supply and destruction of RBC’s. Thalassemia is mostly found in South Asian, Middle Eastern, Chinese, Mediterranean or African origin. Out of total global thalassemic patients, approximately 10% of the thalassemic are from India only. In India, more than 32000 babies are born every year with hemoglobinopathies with carrier frequency of about 3-4 % every year. Thalassemia screening is one of the most essential test for each family to leave a healthy and better life.

The word “Thalassemia” has a Greek origin; thalassa meaning sea and haema meaning blood. It is inherited disorder of blood meaning that can be transfer from one generation to another due to the gene mutation or deletion of certain key genes associated with blood haemoglobin production. Haemoglobin is oxygen carrying protein molecule found in erythrocytes commonly known as Red Blood Cells (RBC). Haemoglobin disorder results in destructions of RBC, leading to anemia. Based on the type of haemoglobin gene involved in the disorder, thalassemia is classified either as alpha-thalassemia (α- thalassemia, HBA) or beta-thalassemia (β-thalassemia, HBB). Compared to alpha-thalassemia, beta-thalassemia is more clinically significant even though latter (1-80%) has higher carrier rate compared to the former (3-17%). >95% of the server β-thalassemia cases are accounted by five common mutation (-IVS 1-5 G → C, IVS 1 -1 G → T, Codon 41/42 (- TCTT), Codon 8/9 and the 619 bp deletion)1.

Genes

HBB (Hemoglobin Subunit Beta)

Indications

Based on severity β-thalassemia can be either thalassemia major (Cooley’s anemia) or thalassemia intermediate.

Thalassemia major generally occurs before child’s second birthday and show sign:

  • Fussiness
  • Paleness
  • Frequent infections
  • Poor appetite
  • Failure to thrive
  • Jaundice, which is a yellowing of the skin or the whites of the eyes
  • Enlarged organs

Thalassemia intermediate is less severe form of β-thalassemia compared to thalassemia major which can be life threatening and requires regular blood transfusion.

Methodology

Polymerase Chain Reaction (PCR) will be performed on patient’s blood isolated genomic DNA (gDNA) for amplification of HBB gene. The amplified HBB gene product is sequenced bi-directionally using Sanger sequencing method.

Detection

  • The method has clinical and analytical sensitivity of 99% for β-thalassemia.
  • Pathogenic variants in regions other than the targeted area will not be detected by this test.
  • Results of molecular analysis should be interpreted in the context of the patient's clinical and/or biochemical phenotype.
  • Following pathogenic variants will be detected by this method

 

   Gene

                             Mutations

 

 

 

 

 

HBB

IVS I-5 ( G > C)

Poly A site (T > C)

Codon 41/42 (-TCTT)

-88 (C > T)

Codon 30 (G > C)

-90 (C > T)

IVS I-1 (G > T/A)

-28 (A > G)

619-bp deletion

Codon 15 (-T)

Codon 8/9 (+G)

HBS 92 (G > C)

Codon 15 (G > A)

HBE 52 (A > T)

Codon 16 (-C)

c-50 A > C

Cap site +1 (A > C)

 

 

Specimen Requirement

Type: EDTA Whole Blood; Infants upto (2 years): 1-2 ml blood; Children & Adults: 3-5 ml blood

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.