Codon 24 (TAT>TAG) and Codon 32 (ATG>AGG) (Hb Rotterdam): Two Novel α2 Gene Mutations Associated with Mild α-Thalassemia Found in the Same Family After Newborn Screening

Abstract

We report two novel α2-globin gene mutations found in the same Surinamese family. The proband, a newborn presenting during neonatal screening with 21.3% Hb Bart's (γ4), proved to be a carrier of the common –α^3.7 deletion and a novel codon 32 (ATG>AGG) transversion that we named Hb Rotterdam. The father carried the same point mutation with borderline hemoglobin (Hb), MCV and low MCH values. The mother presented with a significant microcytic hypochromic anemia and also carried the –α^3.7 deletion and a second novel TAT>TAG transversion generating a stop codon at position 24. Shortly thereafter, Hb Rotterdam was again found in two unrelated adult females and in a Canadian newborn, all of African origin, suggesting that Hb Rotterdam could be a frequently occurring α^T determinant in the Black population. Screening and characterization of the mutations, phenotype/genotype correlation and the issue of reporting newborn carriers of α-thalassemia (α-thal) are discussed.

Keywords:

• Anemia
• α-Thalassemia (α-thal)
• Newborn screening
• Prevention