The linkage of Hb Valletta [?2?287(F3)Thr?Pro] and Hb F-Malta-I [?2 G?2117(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 beta chain. This mutation was found to be linked to that of the gamma chain variant Hb F-Malta-I with a His----Arg mutation at position 117 of the G gamma chain. Both variants were detected in the blood samples of 34 Maltese and two Italian newborn 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 beta-thalassemia heterozygotes) resulted in the detection of two adult Hb Valletta heterozygotes. Dot-blot hybridization analyses of amplified DNA with a probe specific for the G gamma-F-Malta-I variant showed that both also carried that mutation. These results show close linkage of the mutant forms of the G gamma- and beta-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.

Hb Valletta [β87(F3)Thr→Pro] and Hb Marseille/Long Island [β2(NA2)His→Pro; (–1)Met-(+1)Val-(+2)Pro-Leu], in a Unique Compound Heterozygote with a Normal Hemoglobin Phenotype

“…However, silent or hyperunstable variants, rare types of thalassemia and unlinked variants of HPFH could confound diagnosis, particularly in the setting of antenatal diagnosis or neonatal testing. 170 R. Galdies et al Here we describe a young lady from Malta who was found, in the course of postnatal follow-up, to be a compound heterozygote for two electrophoretically silent Hb variants: Hb Valletta or b87(F3)Thr→Pro (1,2) and Hb Marseille, also known as Hb Long Island, or b2(NA2)His→Pro; (-1)Met-(+1) Val-(+2)Pro-Leu (3,4). The identification of the Hb variant was carried out by DNA sequencing.…”

A Review ofCis-TransInterplay Between DNA Sequences 5′ to theGγ- and β-Globin Genes Among Hb F-Malta-I Heterozygotes/Homozygotes and β-Thalassemia Homozygotes/Compound Heterozygotes, and the Effects of Hydroxyurea on the Hb F/F-Erythrocyte; the Need for Large Multicenter Trials

“…Hb F-Malta-I is a stable variant of the G γ-globin gene that is found in tight linkage disequilibrium with the β-globin variant Hb Valletta [β87(F3)Thr→Pro], and occurring in 1.8% of Maltese neonates (17). It is readily detected by IEF and the various globins are quantifiable by HPLC, as described by Kutlar et al (17).…”