A Novel α‐Thalassemia Nonsense Mutation in Codon 23 of the α2‐Globin Gene (GAG→TAG) in a Tunisian Family

Abstract

Herein we describe a novel α‐thalassemia (thal) point mutation in the α2‐globin gene, found in a 3‐year‐old Tunisian girl who had Hb Bart's (γ4) at birth, later on presenting with moderate anemia, microcytosis and hypochromia. She had a normal Hb A2 level and no abnormal hemoglobin (Hb) fraction. After excluding most of the common Mediterranean mutations, the α2‐globin gene was sequenced and found to have a point mutation in the heterozygous state that creates a premature stop signal for translation (GAG→TAG or Glu→Term) at codon 23. The same mutation was also found in the mother in the heterozygous state, while the father had a normal sequence. The presence of the mutation was also confirmed by nucleotide sequencing of the opposite strand. Since the mutation creates a restriction site for the BfaI enzyme, a polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP)‐based assay was established for screening purposes.