Two French Caucasian Families with Dominant Thalassemia-Like Phenotypes Due to Hyper Unstable Hemoglobin Variants: Hb Sainte Seve [Codon 118 (− T)] and Codon 127 [CAG→TAG (Gln→Stop])

Abstract

We report two French Caucasian families suffering from dominant thalassemia-like phenotypes due to hyper unstable hemoglobin (Hb) variants. In both cases, molecular analysis revealed a defect localized in the third exon of the β-globin gene, resulting in dramatic changes of the Hb structure. The first one is a new variant, Hb Sainte Seve, that is associated with a frameshift mutation at codon 118 (− T). In the second family, the disease resulted from a truncated protein due to a stop mutation at codon 127 [CAG →TAG (Gln→Stop)]. These two observations are additional evidences of the important role played by helix H in Hb stability: its partial absence, or a large structural modification, seems to be the major reason for the hyper instability of such molecules.

• Hemoglobin (Hb)
• β-Thalassemia (thal)
• Frameshift
• Nonsense mutation