HEMOGLOBIN LLEIDA - A NEW ALPHA(2)-GLOBIN VARIANT(12 BP DELETION) WITH MILD THALASSEMIC PHENOTYPE

Molecular studies of alpha-thalassaemias have revealed defects at diff erent steps in the process of alpha-gene expression. It is not surpris ing, therefore, that in some cases a single mutation or small deletion can result in a structurally abnormal haemoglobin that produces the a lpha-thalassaemia phenotype. In this report we describe a new unstable alpha-globin variant, Hb Lleida, in a Spanish patient with alpha-thal assaeemia trait. The mutation was detected by single-strand conformati on polymorphism in the third exon of the alpha(2)-globin gene. Direct sequence analysis of the alpha-globin gene showed a 12 bp deletion as the only defect of the alpha(2)- and alpha(1)-globin genes. The propos itus was revealed to be a heterozygous carrier, and two alleles were s eparated by electrophoresis. This deletion causes the loss of four ami noacid residues (from codon 113 to 116) and would be expected to produ ce an unstable haemoglobin, as a shorter alpha-globin chain variant is created with 137 amino acids instead of 141 amino acids present in a normal alpha-globin chain. However, no abnormal haemoglobin was found by either isoelectric focusing or haemoglobin electrophoresis. Since t he deletion affects an aminoacid residue (114 Pro) involved in alpha(1 )-beta(1)-globin chain contacts, the interaction required for efficien t Hb assembly is also compromised. The resulting unstable alpha-globin chain is rapidly catabolized and unsuitable for haemoglobin tetramer formation, causing an alpha-thalassaemia trait phenotype in the hetero zygous patient.