Prenatal Diagnosis and Screening of Thalassemia Mutations in Bangladesh: Presence of Rare Mutations.

Thalassemia is the most common congenital monogenic disorder in Bangladesh. Prenatal diagnosis (PND) and pregnation termination of an affected child is one of the best options to reduce the burden of thalassemic children. This article reports the results of DNA analyses of chorionic villus sampling (CVS) and amniocentesis of fetuses of mothers who came to the thalassemia center of Dhaka Shishu (Children) Hospital, Dhaka, Bangladesh. DNA analysis was done by real-time polymerase chain reaction (qPCR) and Sanger sequencing. Maternal contamination was ruled out by variable number of tandem repeats (VNTRs). A total of 232 samples were analyzed. Hb E (HBB: c.79G>A)/β-thalassemia (Hb E/β-thal) was the most common type of thalassemia seen in 32 samples (13.79%) followed by β-thal major (β-TM) in 10 cases (4.31%). Molecular characterization of the most predominant mutation was IVS-I-5 (G>A) (HBB: c.92+5G>C). The analysis also revealed five rare mutations: IVS-II-654 (C>T) (HBB: c.316-197C>T), IVS-II-1 (G>A) (HBB: c.315+5G>A), codon 44 (-C) (HBB: c.135delC), -86 (C>A) (HBB: c.-136C>A) and codons 14/15 (+G) (HBB: c.45_46insG), which have not been reported previously in Bangladesh. This study provides important information for PND and will help in the development of similar diagnostic programs for other DNA centers in Bangladesh.