Primary Investigator
Rumana Mahtarin
Our Approach
β-thalassemia presents a severe public health challenge in Bangladesh, necessitating urgent and improved molecular techniques for early diagnosis and prevention. To address this, we evaluated a non-invasive prenatal testing (NIPT) pathway utilizing an Amplification Refractory Mutational System- Polymerase Chain Reaction (ARMS-PCR) based method. By isolating cell-free fetal DNA (cff-DNA) circulating in maternal plasma, this approach targets the detection of paternally-inherited β-thalassemia mutations. This screening strategy serves as a safer, non-invasive alternative to traditional, highly invasive sampling procedures like amniocentesis and chorionic villus sampling, effectively bypassing their associated clinical risks.
Research Goals
This evaluation study aims to optimize and establish a conventional ARMS-PCR methodology for detecting paternally inherited β-thalassemia mutations in maternal cell-free DNA and to assess the concordance and technical feasibility of this non-invasive approach against established invasive diagnostic procedures (the gold standard) on a case-by-case basis.
Context
β-thalassemia is a major inherited genetic blood disorder in Bangladesh, with a carrier frequency of approximately 11.89%. Driven in part by high rates of consanguineous marriage, the country faces a massive projected burden of more than 14,000 affected births annually. Managing the disease postnatally through conventional treatments, such as chronic blood transfusions and iron chelation therapy is both logistically challenging and economically devastating for families.
Currently, state-of-the-art prenatal diagnosis relies on invasive sampling techniques to collect amniotic fluid or chorionic villi. However, these procedures carry a 1-2% risk of miscarriage, alongside risks of fetal infection and maternal psychological trauma. While NIPT has successfully revolutionized global screening for chromosomal aneuploidies, its local feasibility for single-gene disorders like β-thalassemia using affordable, PCR-based methodologies remains largely unvalidated within the national healthcare system. A robust local evaluation is essential to develop accessible screening options that mitigate these clinical risks.
Impact
This study lays the groundwork for the development of non-invasive prenatal testing for β-thalassemia in Bangladesh by demonstrating its preliminary technical feasibility. The findings provide important evidence to inform future methodological refinement and implementation efforts. In the long term, incorporation of this approach into national thalassemia control programs could expand access to safer prenatal screening, reduce the need for invasive diagnostic procedures, decrease healthcare costs, and support improved maternal and child health outcomes nationwide.
Funding Source
- Bangladesh Medical Research Council (BMRC)
