β-Thalassemia Due to a Novel Nonsense Mutation at Codon 37 (TGG→TAG) Found in an Afghanistani Family

Abstract

We have identified and characterized a novel β-thalassemic mutation in an Afghanistani family. The molecular pathology consists of a single base substitution (TGG→TAG) at codon 37 of the β-globin gene, giving rise to a stop codon (TAG). Premature stop of translation results in a truncated protein and usually the phenotype of β-thalassemia (thal) major in homozygous individuals. However, this was not the case in our proband, who was homozygous for the codon 37 mutation. He presented with the phenotype of thalassemia intermedia with a hemoglobin (Hb) level of 8.1 g/dL and no previous history of blood transfusions. High performance liquid chromatography (HPLC) analysis showed exclusively Hb F except for a Hb A₂ level within normal limits. Subsequent analysis demonstrated homozygosity for the XmnI ^Gγ polymorphism and heterozygosity for a deletional α-thal (αα/ − α^{− 3.7}). These findings might, at least partly, explain the β-thal intermedia phenotype observed in the proband.

• β-Thalassemia (thal)
• Nonsense mutation
• Codon 37