Characterization Of Beta Thalassaemia Mutations In Patients Having Borderline Haemoglobin A2 Levels.

Area of Science:

• Hematology
• Medical Genetics

Background:

• Single beta thalassaemia allele carriers often present with microcytic hypochromic red blood cells and elevated HbA2.
• Some carriers may exhibit normal or borderline HbA2 levels due to genetic or acquired factors.
• Accurate identification of beta thalassaemia carriers is vital for genetic counseling and population screening.

Purpose of the Study:

• To determine the significance of molecular analysis in individuals with borderline HbA2 levels.
• To assess the utility of molecular testing in a population screening program for beta thalassaemia.

Main Methods:

• A cross-sectional study involving 123 individuals with borderline HbA2 (3-3.9%) was conducted.
• Molecular testing using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) identified common beta thalassaemia mutations.
• Red Blood Cell indices and HbA2 values were compared between beta thalassaemia carriers and non-carriers.

Main Results:

• Beta thalassaemia mutations were detected in 47.1% of individuals with borderline HbA2.
• The most frequent mutations were IVS1-5 and Fr8-9 (15.4% each), followed by Fr41-42 (6.5%).
• Individuals with mutations showed significantly lower Mean Corpuscular Volume (MCV) and Mean Corpuscular Haemoglobin (MCH) (p<0.001).
• Mutations were more prevalent in the 3.5-3.9% HbA2 range (63.8%) compared to the 3-3.4% range (36.2%) (p<0.001).

Conclusions:

• Molecular testing is pivotal for confirming beta thalassaemia carriers with borderline HbA2 levels in high-prevalence regions like Pakistan.
• Molecular testing for beta thalassaemia should be offered to individuals with borderline HbA2 (3.4-3.9%) and microcytic hypochromic indices.