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

Abstract

We have identified and characterized a novel beta-thalassemic mutation in a North African adult. The molecular defect consists of a two nucleotide (nt) deletion in the beta-globin gene at codon 76 [beta76 (-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 beta-globin gene and none of the more common known deletions in the alpha-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 beta-thalassemia (thal). This is the first example of a premature stop codon at position 89.

Elevated Hemoglobin A2 as a Marker for .BETA.-Thalassemia Trait in Pregnant Women

“…The second group had no iron deficiency or microcytic anemia with HbA2 level < 3.5%, and were excluded β-thalassemia mutation based on no β-thalassemia history, normal complete blood count and RDB assay. For samples with HbA2 level between 3.0% and 3.5%, and none of the 18 known β-thalassemia mutation detected by RDB assay, direct sequencing of the human β-globin gene was performed to make sure there were no β-thalassemia mutations (Foulon et al 2007). The data were subjected to statistical analysis using SPSS 16.0 software.…”

Compound heterozygote condition in beta thalassemia major due to a novel single nucleotide deletion (–T) at codon 69 in association with IVS 1‐5 (G>C) mutation

“…This mutation leads to deletion of single nucleotide in the codon 69, which causes frameshift and stop codon at position 88. This can be hypothesized to lead to nonsense-mediated mRNA decay and hence a null phenotype (Foulon, Rochette & Cadet, 2007;Ghedira et al, 2011;Frischknecht et al, 2009). Although there has been a case report from China, showing dominant inheritance of beta thalassemia in association with frameshift mutation at codon 53 (Yi et al, 2008), the family reported by us clearly shows recessive inheritance pattern.…”

“…This mutation leads to deletion of single nucleotide in the codon 69, which causes frameshift and stop codon at position 88. This can be hypothesized to lead to nonsense‐mediated mRNA decay and hence a null phenotype (Foulon, Rochette & Cadet, 2007; Ghedira et al. , 2011; Frischknecht et al.…”