Delineation of the Molecular Basis of #{246}- and Normal HbA2 9-Thalassemia

In this study, we used cloning and sequence analysis to define the molecular defect in two -thaIassemia genes. one associated with reduced output of #{244}-globin chains ( +th9I) from a Sardinian and the other with a complete supression of #{246}-chain production from the affected locus ( “tls’) from a Southern Italian. Sequence analysis of the 15+th.I gene showed a GT substitution at the first nucleotide of codon 27 (6+27) which produces an amino acid change (AlaSer) and presumably activates a cryptic splice site located at this position. Therefore, only a fraction of the transcript is processed from this site, as indicated by the clinical phenotype of . DNA sequencing of the #{212} gene revealed a T-C substitution at