ABSTRACT
OBJECTIVES: α-thalassemias are caused by a deficiency in or absence of synthesis of the α-chain of haemoglobin (Hb). In contrast, structural haemoglobinopathies are due to mutations that change the amino acid sequence of the protein chain. We report 4 newly identified α-chain Hb variants. Two variants were hyper-unstable, whereas the other 2 were structural variants with an altered electrophoretic mobility. DESIGN AND METHODS: The first 2 families were identified because of microcytosis and hypochromia with a normal Hb A2 and Hb F but without iron deficiency. The other 2 families came to scrutiny because of a peak of abnormal Hb during routine analytical assays. These Hb variants were characterized by specific sequencing. RESULTS: The hyper-instability of Hb Cervantes is probably due to its lower affinity for the alpha chain haemoglobin-stabilizing protein (AHSP). Hb Marañón is another unstable Hb variant that produces an α-thalassemia phenotype. For the identification of Hb La Mancha, a molecular characterization by sequencing was required. Finally, Hb Goya was found to have the same electrophoretic mobility as Hb J. A lower percentage of the variant was obtained due to a possible component of instability, though the patient did not show evidence of anaemia. CONCLUSION: These variants of Hb add to the variety and complexity of disorders of the genes that encode Hb.
