Hb Filottrano [codon 120 (–A)]: A Novel Frameshift Mutation in Exon 3 of the β-Globin Gene Causing Dominantly Inherited β-Thalassemia Intermedia

Abstract

We report a novel frameshift mutation in exon 3 of the β-globin gene, that, in the heterozygous state, leads to a β-thalassemia intermedia (β-TI) phenotype (marked anemia, splenomegaly, hyperbilirubinemia, jaundice, unbalanced synthesis of α/non-α chains in a 34-year-old Italian woman. This frameshift mutation, due to the deletion of the first nucleotide (–A) at codon 120, results in a β-globin chain that is elongated to 156 amino acid residues. These highly unstable abnormal chains precipitate in the erythroblasts as inclusion bodies, thus causing inefficient erythropoiesis and ultimately resulting in the observed dominant clinical phenotype.

• Dominant β-thalassemia intermedia (β-TI)
• Inclusion bodies
• Elongated chain
• Abnormal hemoglobin (Hb) variant

ACKNOWLEDGMENTS

The presentation of this study gives us the opportunity to remember the late Professor Ida Bianco Silvestroni [Associazione Nazionale lotta contro le Microcitemie in Italia (ANMI Onlus), Rome, Italy] who first made the diagnosis of β-TI in these described clinical cases in 1981. We thank Professor Alessia Colosimo (Department of Comparative Biomedical Sciences, University of Teramo, Teramo, Italy) for expert assistance in the preparation of this manuscript.

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