Novel α2 Gene Deletion (c.349_359 del GAGTTCACCCC) Identified in Association with the –α^3.7 Deletion

Abstract

We report a novel α2 gene mutation identified in compound heterozygosity with the common –α^3.7 deletion. The mutation (c.349_359 del GAGTTCACCCC), causes a frameshift after codon α115 with the predicted extension of the αchain from 141 to 166 residues. The new polypeptide would be expected to have a mass of 17,463 Da, but no such product was detected in hemolysates, confirming the mutation’s thalassemic phenotype. Mechanistically, the deletion is probably caused by replication slippage during DNA synthesis as the sequence is bracketed by a CC repeat. The lack of protein expression is probably caused by loss of critical binding sites to the chaperone, α Hb stabilizing protein (AHSP).

• Hemoglobin (Hb) extension
• Replication slippage
• α-Thalassemia (α-thal)
• α Hb stabilizing protein (AHSP)