α-Thalassemia Phenotype Induced by the New IVS-II-2 (T→A) Splice Donor Site Mutation on the α2-Globin Gene

Abstract

We present a family of North European extraction referred for a refractory non iron depleted microcytic anemia. The proband, a 36-year-old male, presented with chronic borderline anemia and microcytic hypochromic parameters. No abnormal hemoglobin (Hb) fractions were observed on high performance liquid chromatography (HPLC) or on alkaline electrophoresis. Gap-polymerase chain reaction (gap-PCR) excluded the seven common α-thalassemia (thal) deletion defects. However, the β/α-globin chain synthesis ratio measured in vitro was unbalanced, indicating a reduced expression of the α-globin genes. Direct sequencing of the α-globin genes revealed heterozygosity for a T→A transversion at the IVS-II-2 position of the α2 gene. This is the first IVS-II splice donor site mutation described on the α2-globin gene.

Keywords:

• α Genes
• Thalassemia (thal)