Mapping the Mutation Spectrum in Prenatal Thalassemia: Insights from a Tertiary Care Center in Delhi

Background: Understanding ethnic and region-specific mutations helps in creating customized molecular testing panels, enabling accurate and timely prenatal diagnosis of thalassemia to prevent the birth of affected children. Materials and Methods: A retrospective analysis was conducted on data from 338 high performance liquid chromatography (HPLC) screen positive beta thalassemia-positive individuals (162 couples) and 14 mothers who were referred to Lok Nayak Hospital, New Delhi, for thalassemia diagnosis between 2016 and 2022. Initially, ARMS PCR for targeted five prevalent mutations in the ß-globin gene, followed by whole gene molecular sequencing of HBB was done. Chorionic villus sampling was later performed for prenatal diagnosis of 144 fetuses from 144 couples. Result: Among 482 tested individuals, the most common mutations in the cohort were IVS 1-5 {G>C} (53.11%), codon 41-42 {–CTTT} (11.20%), codon 8/9 {+G} (8.7%), Codon 26{G>A} (5.3%), and codon 16 {-C} (5.1%). Less frequent mutations included IVS 1:1{G>T}, 619 bp deletion, and Hb S (A>T), comprising 3.7%, 2.9%, and 1.8% respectively. Conclusion: While PCR-based mutation-specific sequencing is reliable for screen-positive couples, whole HBB gene sequencing is more cost-effective and recommended for identifying all thalassemia mutations, including rare ones. Key words: Thalassemia screening, Prenatal diagnosis, Chorionic villus sampling, HBB gene sequencing.