The linkage of Hb Valletta [α2β287(F3)Thr→Pro] and Hb F-Malta-I [α2Gγ2117(G19)His→Arg] in the Maltese population

Abstract

We have identified a new stable abnormal hemoglobin called Hb Valletta, which is characterized by a Thr→Pro substitution at position 87 of the β chain. This mutation was found to be linked to that of the γ chain variant Hb F-Malta-I with a His→Arg mutation at position 117 of the Gγ chain. Both variants were detected in the blood samples of 34 Maltese and two Italian new-born babies with isoelectrofocusing and reversed phase high performance liquid chromatography. Similar analyses of cord blood from 388 additional Maltese newborns failed to identify either one of these two variants. Additional analyses of 353 Maltese adults (including 39 β-thalassemia heterozygotes) resulted in the detection of two adult Hb Vallettaheterozygotes. Dot-blot hybridization analyses of amplified DNA with a probe specific for the Gγ-F-Malta-I variant showed that both also carried that mutation. These results show close linkage of the mutant forms of the Gγ- and β-globin genes, 27–28 kb apart, and a failure to identify chromosomes with either the Hb F-Malta-I mutation alone or with the Hb Valletta mutation alone, indicating a low recombination frequency.