^Gγ −37 (A→T): A New Nondeletional Hereditary Persistence of Fetal Hemoglobin Determinant Associated with the Rare Codon 91 (+T) δ⁰-Thalassemia

Abstract

We recently described a rare frameshift mutation in the δ-globin gene in a Dutch patient, in association with a new mutation of the ^Gγ-globin gene promoter [^Gγ −37 (A→T)] with a moderately elevated Hb F level of 2.3%. The δ mutation at codon 91 (+T) has been described once before in our laboratory in 1989, in a complex Belgian family with ^Gγ (^Aγδβ)⁰-thalassemia (thal) and moderately elevated Hb F levels, without the ^Gγ (^Aγδβ)⁰-thal deletion in some individuals. Analysis of the patients from 1989 revealed the presence of the same ^Gγ-globin gene mutation and moderately elevated Hb F in all patients, who were also carriers of the δ-globin gene frameshift. Further analysis demonstrated that the two mutations were in linkage with the same haplotype in both the Belgian family and the recently found patient, confirming the association of the elevated Hb F expression with the new ^Gγ-globin gene mutation.

Keywords:

• Hb A₂
• Hb F
• δ-Thalassemia (thal)
• Nondeletional hereditary persistence of fetal hemoglobin (HPFH)
• Hemoglobin (Hb)