Delta globin gene variations leading to reduction in HbA₂ levels

Area of Science:

• Hematology
• Molecular Genetics

Background:

• Beta-thalassaemia trait diagnosis can be complicated by co-inherited delta-globin gene variants.
• These variants, while not pathogenic alone, can alter haemoglobin levels, potentially masking the underlying condition.

Observation:

• This case study presents two patients with beta-thalassaemia trait and co-existing delta-globin gene mutations.
• One patient had a beta-thalassaemia trait (IVS 1-5G→C) with a low HbA2 level (1%) and a delta-globin gene variant (HbA2 St. George CD 81).
• Another patient exhibited near-absent HbA2 levels due to a delta-globin gene mutation (HbA2 Saurashtra CD 100) and an alpha-globin gene deletion.

Findings:

• The study highlights specific delta-globin gene variants (HbA2 St. George CD 81 and HbA2 Saurashtra CD 100) that interact with beta-thalassaemia trait.
• These interactions lead to altered HbA2 levels, complicating diagnostic interpretation.

Implications:

• Increased awareness and detection of delta-globin gene mutations are vital in regions with high beta-thalassaemia prevalence.
• Accurate diagnosis of beta-thalassaemia carriers requires considering complex interactions between different haemoglobinopathies.