Estelle Cadet

First Identification of a Point Mutation at Position −83 (G>A) of the β-Globin Gene Promoter

We report the first identification of a point mutation located within the promoter region of the β‐globin gene at position −83 (G>A) and associated with the common heterozygous deletional α‐thalassemia (α-thal) (−α3.7/αα). The patient was an adult male from Gabon belonging to the Obamba sub ethnic group, who was referred to our clinics for a mild microcytic anemia with a Hb A2 level at the upper limit of the normal value (3.5%). This observation is a new example of α- and β-thal co-inheritance with a normal Hb A2 level, and illustrates a potential source of pitfall in screening for α- and β-thal carriers.

A New Intergenic α-Globin Deletion (α–αΔ125) Found in a Kabyle Population

Abstract We have identified a deletion of 125u2009bp (α–αΔ125) (NG_000006.1: g.37040_37164del) in the α-globin gene cluster in a Kabyle population. A combination of singlex and multiplex polymerase chain reaction (PCR)-based assays have been used to identify the molecular defect. Sequencing of the abnormal PCR amplification product revealed a novel α1-globin promoter deletion. The endpoints of the deletion were characterized by sequencing the deletion junctions of the mutated allele. The observed deletion was located 378u2009bp upstream of the α1-globin gene transcription initiation site and leaves the α2 gene intact. In some patients, the α–αΔ125 deletion was shown to segregate with Hb S (HBB: c.20A>T) and/or Hb C (HBB: c.19G>A) or a β-thalassemic allele. The α–αΔ125 deletion has no discernible effect on red cell indices when inherited with no other abnormal globin genes. The family study demonstrated that the deletion is heritable. This is the only example of an intergenic α2-α1 non coding DNA deletion, leaving the α2-globin gene and the α1 coding part intact.