Unusual Molecular Basis of Hb H Disease in the Azores Islands, Portugal

Abstract

An Azorean family with Hb H disease (10% Hb H) was studied in order to elucidate its molecular basis. DNA studies on the patient only revealed a 4.2 kb “leftward” deletion of paternal origin which implies the co-inheritance of a nondeletional α-thal-assemia determinant. Restriction endonuclease and oligonucleotide analysis allowed the exclusion of five point mutations: initiation codon (at both αl- and α2-globin genes), IVS-I donor splice junction pentanucleotide deletion, codon 125 CTG→CEG substitution, and Saudi Arabian polyadenylation signal mutation. These findings suggest that the molecular basis of this form of Hb H disease is probably different from those described previously.