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The molecular basis of β-thalassemia (β-thal) mutations in North and in South Vietnam have been described during the past 15 years, whereas limited data were available concerning the central area of the country. In this study, we describe the molecular characterization and frequency of β-globin gene mutations in the Thua Thien Hue Province of Central Vietnam as the result of a first survey conducted in 22 transfusion-dependent patients, and four unrelated heterozygotes. Nine different known mutations were identified (seven of the β 0 and two of the β + type) in a total of 48 chromosomes. The most common was codon 26 (G>A) or Hb E (HBB: c.79 G>A) accounting for 29.2% of the total studied chromosomes, followed by codon 17 (A>T) (HBB: c.52 A>T) (25.0%), and codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) (18.8%). Other mutations with appreciable frequencies (6.3-8.3%) were IVS-I-1 (G>T) (HBB: c.92+1 G>T), codon 26 (G>T) (HBB: c.79 G>T) and codons 71/72 (+A) (HBB: c.216_217insA). Relatively rarer (2.0%) were the promoter -28 (A>G) (HBB: c.78 A>G) mutation, the codon 95 (+A) (HBB: c.287_288insA), which is reported only in the Vietnamese, and the codons 14/15 (+G) (HBB: c.45_46insG) mutation, thus far observed only in Thailand. Results are relevant for implementing appropriate measures for β-thal prevention and control in the region as well as in the whole country.

Here we describe Hb F-Avellino [(G)γ41(C7)Phe → Leu; HBG2: c.124 T > C], a new hemoglobin (Hb) variant observed in a healthy newborn. The proband's hemolysate was found to be mildly unstable by the isopropanol test. The occurrence of the variant was assessed by both chromatographic and electrophoretic methods. DNA sequencing analysis of the (G)γ gene showed a T to C transition at codon 41 (TTC > CTC) corresponding to the Phe → Leu substitution. Normal functional properties have been hypothesized.

We report a new hemoglobin (Hb) variant on the HBA2 gene, Hb Zara [α91(FG3)Leu→Ile (α2); HBA2: c.274C > A], which was found in a Caucasian man from Croatia. It was observed by routine cation exchange chromatography as an abnormal 21.8% fraction overlapping Hb A2, and associated with normal hematology. It was slightly unstable by the standard isopropanol precipitation test. DNA analysis revealed the CTT > ATT mutation at codon 91 on an α2 gene of a normal α-globin gene arrangement. This new variant represents the sixth described mutation at codon α91 and fourth on the α2 locus. As a result of the slight instability due to the significant role of the α91 residue in the α1β2 contact, the level of the Hb Zara variant was lower than levels observed for several stable variants codified by the α2 locus.

Two healthy newborns, heterozygous for two different gamma-globin chain mutations, were observed during an electrophoretic screening for hemoglobinopathies in Sassari, North Sardinia (Italy). The variants were characterized by reversed phase high performance liquid chromatography (HPLC) and sequencing of amplified gamma-globin genes. One of the two abnormalities was a novel (A)gammachain variant and the tetramer was named Hb F-Osilo [(A)gamma119(GH2)Gly-->Ser]. The other was a (G)gamma chain variant, Hb F-Paulinia [(G)gamma80(EF4)Asp-->Tyr], already described in a Brazilian baby of African ancestry. No functional studies could be performed.

Hb F-Emirates [Ggamma59(E3)Lys --> Glu] was first described in a newborn from the United Arab Emirates. Here we describe the occurrence of this variant in a family of Sardinian ancestry. Direct DNA sequencing analysis of the selectively amplified Ggamma gene shows that the AAA --> GAA transition, corresponding to a Lys --> Glu substitution, is responsible for this abnormal hemoglobin (Hb). Our observation indicates a multiple origin of the mutation. In order to facilitate future studies at the level of population genetics, the structure of the entire Ggamma gene that carries the mutation was assessed and compared with that of normal Ggamma genes.

The abnormal Hb F-Porto Torres [Agamma75(E19)Ile-->Thr, 136(H14)Ala-->Ser] was observed during a cord blood survey for hemoglobinopathies in North Sardinia. This silent variant showed the same mobility as Hb F-Sardinia in isoelectric focusing (IEF) of the tetramers, whereas the abnormal globin chain was clearly separated by acid-urea-Triton polyacrylamide gel electrophoresis (AUT-PAGE) from the normal Ggamma- and Agamma-globin chains. Separation of the globin chains by reversed phase high performance liquid chromatography (HPLC) indicated the following percentages: Ggamma 68.4, Agamma 14.0, Xgamma 17.6, that strongly suggested the abnormal chain as being a variant of the Agamma-globin. Sequencing of the gamma-globin genes indicated that the mutated gene was in fact an Agamma with two nucleotide replacements, one being the ATA-->ACA (Ile-->Thr) at codon 75 (the so-called AgammaT of the rather common Hb F-Sardinia) and the second the GCA-->TCA (Ala-->Ser) at codon 136. This new variant is the seventh having the sequence of the AgammaT chain with an additional mutation so far described and the third characterized by gene sequencing.