A Novel Pathogenic Beta-Thalassemia Mutation Identified At Codon 8 (Hbb: C.27delg) In A Bangladeshi Family Acquired De Novo

In Bangladesh, the practice of beta-thalassemia (beta-thal) carrier screening and prenatal diagnosis (PND) by beta-globin gene sequencing has been initiated to prevent the birth of affected children. The study aimed to describe a novel de novo mutation of the beta-globin gene and its clinical implication. Out of 100 Bangladeshi beta-thal carrier families, one patient with hematological and clinical features associated with beta-thal and her parents were included. Molecular characterizations of beta-globin gene mutations were performed by direct sequencing. A novel nucleotide deletion mutation at codon 8 in the first exon of the beta-globin gene (HBB: c.27delG) was found in a 1-year-old child of the studied family in a heterozygous state along with common Hb E (HBB: c.79G>A). The mutation caused a frameshift to a new stop codon at codon 18 resulting in a beta(0)-thal phenotype. The proband exhibited a beta-thal intermedia (beta-TI)-like genotype, however, showed beta-thal major (beta-TM)-like complications and was transfusion-dependent. Her mother had a profile consistent with the Hb E trait, while the father had normal hematological indices. Mutation analyses revealed the mother to be heterozygous for Hb E, while the father had a normal genotype. The novel mutation was assumed to be inherited de novo by the paternity test. The study documented a novel pathogenic mutation in the beta-globin gene in a Bangladeshi family by beta-globin gene sequencing.