A Novel Pathogenic β-Thalassemia Mutation Identified at Codon 8 (HBB: c.27delG) in a Bangladeshi Family Acquired De Novo

Abstract

In Bangladesh, the practice of β-thalassemia (β-thal) carrier screening and prenatal diagnosis (PND) by β-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 β-globin gene and its clinical implication. Out of 100 Bangladeshi β-thal carrier families, one patient with hematological and clinical features associated with β-thal and her parents were included. Molecular characterizations of β-globin gene mutations were performed by direct sequencing. A novel nucleotide deletion mutation at codon 8 in the first exon of the β-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 β⁰-thal phenotype. The proband exhibited a β-thal intermedia (β-TI)-like genotype, however, showed β-thal major (β-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 β-globin gene in a Bangladeshi family by β-globin gene sequencing.

Keywords:

• β-Thalassemia (β-thal)
• novel de novo mutation
• sequencing analysis

Acknowledgements

We gratefully acknowledge the assistance and support from the specialist physician and the laboratory staff of DNA Solution Ltd. during the collection of samples from participants. We are grateful to all Bangladeshi families who gave their consent to participate in this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.