A Rare 33 bp In‐Frame Deletion (α63–74 or α64–74 or α65–75) in the α1‐Globin Gene Causing α⁺‐Thalassemia: A Second Observation

Abstract

The most frequent defects resulting in α‐thalassemia (thal) include large deletions that remove one or both of the duplicated α‐globin genes on chromosome 16. Less commonly, α‐thal mutations involve single nucleotide substitutions or micro deletions, leading either directly to decreased α‐globin chain synthesis by the affected allele, or indirectly through production of hyperunstable variant α‐globin chains. Here we describe the characterization of a 33 bp in‐frame deletion within the α1‐globin gene, in a woman with hematological findings consistent with an α‐thal trait. The amino acids predicted to be missing as a result of the 33 bp deletion are at the end of the E helix and the EF corner of the α‐globin protein chain, and are not normally involved in the heme contact, although it is presumed that α‐globin chain folding and hemoglobin (Hb) formation will be disrupted. The observation of inclusion and Heinz bodies indicates the synthesis of some abnormal Hb (or globin chains). An identical mutation has been previously observed in a single case, a Canadian individual of Greek descent, indicating that it is a rare mutation, and probably of the same origin. Possible mechanisms underlying the mutation at the DNA level are discussed.

• 33 bp In‐frame deletion
• α1‐Globin gene
• α‐Thalassemia
• Hemoglobin (Hb)