Hb Zoetermeer: A New Mutation on the α2 Gene Inducing an Ala→Ser Substitution at Codon 21 is Possibly Associated with a Mild Thalassemic Phenotype

Abstract

A 52-year-old Dutch male was referred to our laboratory for hemoglobinopathy analysis because of persistent microcytic hypochromic parameters and moderate erythrocytosis in the absence of iron deficiency. The hemoglobin (Hb) pattern was normal and breakpoint polymerase chain reaction (PCR) excluded the six common deletion defects of the α gene cluster. Direct sequencing revealed a GCT→TCT transversion at codon 21 of the α2 gene generating an Ala→Ser single amino acid substitution. The hematological parameters observed in the presence of this mutation are consistent with a compensated heterozygous α⁺-thalassemia (thal). However, the neutral mutation and the external position of the residue do not explain an association with this phenotype. Nevertheless, we cannot exclude that the mutation could induce the observed hematological abnormalities and could eventually be considered as a mutation associated with a mild α-thalassemic phenotype.

Keywords:

• Thalassemia
• Abnormal hemoglobins (Hbs)