ALBERT

Beschreibung: Three new Hb variants were found in four blood donors, which we named Hb Itapira [α30(B11) Glu→Val)], Hb Bom Jesus da Lapa [α30(B11) Glu→Ala)] and Hb Boa Esperança [α16 (A14) Lis→Thr], according to their carriers’ origin. The first one was detected in a Caucasian man from Southeastern Brazil; electrophoresis at alkaline pH showed a low proportion Hb S-like band (5,5%), which was not distinguished from Hb A at acidic pH. High performance liquid chromatography-HPLC exhibited a short peak at D-Window. The abnormal α-globin was demonstrated by globin-chain electrophoresis at acid pH, with a slower migration than the normal α-chain. The α genes were sequenced (ABI PRISM-377-DNA automated sequencer, Applied Biosystems, CA, USA) and a base substitution found at the 30th codon of the α1-gene (GAG→GTG), in heterozygosis, causing Glu→Val replacement in the α-chain. Familial analysis revealed that the carrier’s mother and brother have the same alteration. All the affected members of this family are also heterozygous for the α-globin gene triplication (αααanti3.7), explaining the low percentage of the variant and suggesting an association of the mutation with the triplicate haplotype. Hb Bom Jesus da Lapa results of a mutation at the same gene and position: α1, 30th codon (GAG→GCG), causing Glu→Ala replacement. It was detected in an African descendant woman from the northeastern region of Brazil; the electrophoretic behaviour was similar to that of Hb Itapira, but it eluted with Hb A2 on HPLC, in a total of 24.8%, and the mutant did not separate from normal α-chain at the acidic globin electrophoresis. Two other variants with replacement of the α-chain 30th residue have been described [Hb O-Padova (Glu→Lys), found in Italian, Turkish and Spanish families, and Hb G-Chinese (or G-Honolulu, G-Hong Kong, G-Singapore) (Glu→Gln), encountered in Chinese families], none of them with clinical or hematological manifestations although this residue is involved in the αlβ1 contacts of the molecule. Hb Boa Esperança was detected in two apparently not-related individuals, one of them of African descent, both originate from the state of Minas Gerais, Southeast Brazil. This variant moved faster than Hb A at alkaline pH, was not distinguished at acid pH, and eluted as an additional peak at P3 on HPLC (25%); globin-chain electrophoresis showed a slower α-chain. Sequencing revealed a base substitution at the 16th codon of the α2-gene, in heterozygosis (AAG→ACG; Lys→Thr). Although the carriers have different surnames and do not know each other, β-cluster haplotypes are suggestive of a common ancestor. Three other mutations have already been described in this position [Hb I (Lys→Glu), Hb Beijing (Lys→Asn), in asymptomatic heterozigotes, and Hb Harbin (Lys→Met), slightly unstable, resulting in anemia to its carrier. All the three variants described here showed normal instability and solubility tests.