Advanced molecular approaches to thalassemia disorder and the selection of molecular-level diagnostic testing in resource-limited settings

Abstract

Beta-thalassemia is a genetic disorder that significantly burdens healthcare systems globally. This inherited blood disorder, categorized into beta-thalassemia and alpha-thalassemia, results in insufficient globin production, leading to anemia and iron overload from frequent transfusions. Severe cases, known as thalassemia major, require regular blood transfusions. Beyond clinical suspicion and biochemical tests, molecular techniques are essential for confirming the diagnosis and guiding treatment. Advanced molecular profiling methods such as Polymerase Chain Reaction (PCR), Multiplex Ligation-dependent Probe Amplification (MLPA), Next-Generation Sequencing (NGS), Third-Generation Sequencing (TGS), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are effective in detecting mutations. Epigenetic factors also play a crucial role, driving the development of epidrugs for targeted therapy. This review covers various molecular techniques, established gene-editing methods, epigenetic mechanisms, and the impact of artificial intelligence on thalassemia management. It highlights the importance of selecting precise and sensitive molecular tools for detecting thalassemia gene mutations and stresses the need to make these testing methods accessible in resource-limited clinical settings.

Keywords: Epigenetics; Gene editing; QPCR; Sequencing; Thalassemia.

Figure 1

Illustration of the different molecular tools for diagnosis of thalassemia.