Hb Souli, a 6 bp in-frame deletion on the HBA2 gene (HBA2: c.[41-46delCCTGGG]) leads to α-thalassemia intermedia, when in trans to a single α-globin gene deletion.

ABSTRACT

We report the case of a 5-year-old child with clinical and hematological findings consistent with the diagnosis of α-thalassemia intermedia (α-TI). Molecular analysis disclosed the common 3.7 kb deletion in the α-globin gene cluster in trans to a novel in-frame 6 bp deletion in the HBA2 gene. It removes the sequence CCTGGG (or GCCTGG) that normally encodes for alanine (codon 13) and tryptophan (codon 14). Even though several hemoglobin (Hb) variants with mutations affecting codons 13 or 14 have been described, Hb Souli (HBA2 c.[41-46delCCTGGG]) is, to the best of our knowledge, the first variant to be reported where both amino acid residues, α13Ala and α14Trp, are deleted, leading to unstable and rapidly degraded α-globin chains.