A BASE SUBSTITUTION (T-]C) IN CODON-29 OF THE ALPHA-2-GLOBIN GENE CAUSES ALPHA-THALASSEMIA

We have identified three individuals of Greek or Greek Cypriot origin with an atypical form of HbH disease characterized by a severe hypochr omic microcytic anaemia associated with relatively small amounts of Hb H in the peripheral blood. Molecular analysis has shown that each is a compound heterozygote for a previously described mutation affecting t he poly A addition signal (AATAAA-->AATAAG) and a previously undescrib ed mutation involving a T-->C transition in codon 29 of the alpha2 gen e causing a leucine-->proline substitution. Although this mutation wou ld be expected to produce an unstable haemoglobin and hence a haemolyt ic anaemia, simple heterozygotes for the alpha29Leu-->Pro mutation hav e the phenotype of alpha-thalassaemia trait.