A Novel β-Thalassemic Allele Due to a Two Nucleotide Deletion: β76 (−GC)

Abstract

We have identified and characterized a novel β-thalassemic mutation in a North African adult. The molecular defect consists of a two nucleotide (nt) deletion in the β-globin gene at codon 76 [β76 (−GC), c.229–230delGC]. This frameshift mutation generates a TGA stop codon at position 89. The carrier presented with mild microcytic anemia (Hb 12.8 g/dL, MCV 60 fL), no detectable Hb F, an elevated Hb A₂ level (5.5%) with no other mutation in the β-globin gene and none of the more common known deletions in the α-globin cluster. No abnormal hemoglobin (Hb) was present in routine electrophoresis or in high performance liquid chromatography (HPLC) analyses. Pathologic inclusions were absent in both mature red cells and in reticulocytes. This observation reinforces the hypothesis that nonsense and frameshift mutations that result in a premature stop codon in exon 1 or exon 2 inherited in the heterozygous state do not generate dominant β-thalassemia (thal). This is the first example of a premature stop codon at position 89.

Keywords:

• β-Globin gene
• β76 (−GC)
• Frameshift
• Stop codon
• β-Thalassemia (thal)