1/9. Hb zoeterwoude [beta23(B5)Val-->Ala)]: a new beta-globin variant found in association with erythrocytosis.We describe the characterization of a new hemoglobin (Hb) variant found in a 77-year-old Dutch woman, suspected of hypoxia-mediated erythrocytosis. The typical blood parameters (Hb 17.3 g/dL; PCV 0.525 L/L; RBC 5.82 x 10(12)/L) could not be explained by any of the pathological or physiological conditions causing erythrocytosis. The patient was preventively phlebotomized because of intermittent claudication and erythrocytosis. At the hematological and biochemical levels, no anemia or hemolysis were present and no abnormal Hb fractions were detectable on alkaline electrophoresis or high performance liquid chromatography (HPLC). Molecular analysis revealed intact alpha-globin genes and a heterozygosity for a GTT-->GCT transition at codon 23 of the beta-globin gene, causing a Val-->Ala amino acid substitution. The P50 measured in full blood indicated that this mutant has an elevated oxygen affinity. This is the fourth single nucleotide substitution at codon 23 of the beta gene and the second associated with erythrocytosis. Because the family was not available for investigation no information was obtained as to whether the mutation represents a de novo event or was inherited, and might be a more common cause of erythrocytosis in Dutch patients. Considering the relatively high frequency of beta-thalassemia (thal) in the large allochthonous population in The netherlands, combinations of Hb Zoeterwoude and beta-thal traits may lead to hemizygosity, with severe hypoxia and erythrocytosis from a few months after birth.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/9. Hb La Coruna [beta38(C4)Thr-->Ile]: a new hemoglobin variant leading to familial polycythemia.Hb La Coruna [beta38(C4)Thr --> Ile] is a new hemoglobin (Hb) variant that has an increased oxygen affinity. Clinically, this Hb leads to erythrocytosis. Hb La Coruna is an electrophoretically silent variant that can be detected by reversed phase high performance liquid chromatography (HPLC) and characterized by dna sequencing. The patient was a 22-year-old Spanish male whose family lived in La Coruna, in the northwest of spain. His mother was also a carrier.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/9. A case of the Hb Regina (beta 96 (FG3) LeuVal) in a German male associated with high oxygen affinity and erythrocytosis. Hb Regina was identified in a 58-year-old German male and 2 of his 3 children. All affected subjects presented moderate erythrocytosis and the whole blood exhibited increased oxygen affinity (P50:17.5 mm Hg). This hemoglobinopathy was undetectable with the conventional electrophoretic methods. It was, however, separated and quantified by cation-exchange and reverse-phase high-performance liquid chromatography. Hb Regina accounted for 30-35% of the total Hb. No significant clinical symptoms were found to be related to this hemoglobinopathy. This is the first known instance in germany, and so far the second case reported.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/9. A third instance of the high oxygen affinity variant, Hb Heathrow [beta 103(G5)Phe- greater than Leu]: identification of the mutation by mass spectrometry and by dna analysis.Hb. Heathrow [beta 103(G5)Phe- greater than Leu] was identified in an Englishman with a life-long history of polycythemia, his father had been similarly affected. A hemoglobin variant was suspected from the high oxygen affinity of the patient's blood. The Hb Heathrow abnormal beta chain was resolved from the normal beta chain by high performance liquid chromatography, and the abnormal peptide and the amino acid replacement were identified by mass spectrometry. The corresponding base change (C- greater than G at codon 103) was demonstrated by sequence analysis of the polymerase chain reaction amplified exon 2 of the genomic beta-globin gene. This is only the third known instance of Hb Heathrow.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/9. Hb Johnstown [beta 109 (G11) ValLeu]: a new electrophoretically silent variant that causes erythrocytosis. A high oxygen affinity hemoglobin, previously undescribed, was found in a healthy, asymptomatic patient with mild erythrocytosis and left-shifted hemoglobin-O2 dissociation curve. The hemoglobin variant could not be distinguished from Hb A by any of several electrophoretic methods nor by ion exchange chromatography. It was separated and analyzed by reversed phase high performance liquid chromatography. Structural analysis revealed the substitution beta 109 (G11) Val Leu. The variant was named Hb Johnstown. The amino acid substitution perhaps disrupts alpha 1 beta 1 contacts in the deoxyhemoglobin conformation, thus shifting the equilibrium towards the high affinity oxyhemoglobin conformation.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
6/9. Hemoglobin Pierre-Benite [beta 90(F6)GluAsp], a new high affinity variant found in a French family. Hemoglobin Pierre-Benite [beta 90(F6)Glu |
Asp] is a new high affinity variant (P50 = 21.5 mm Hg), with normal heme-heme interaction, found in a French family. It was difficult to detect by conventional electrophoretic methods. However, the high performance liquid chromatography profile of its tryptic peptides contained an additional peak. Amino acid analysis of the corresponding peptide and determination of its sequence allowed us to identify the mutation. No instability was found. Mutations previously recorded in position 90 of the beta-chain display a positive charge shift and a reduced affinity for oxygen, whereas Hb Pierre-Benite shows no charge shift and increased affinity for oxygen. |
7/9. Hb Linkoping (beta 36 ProThr): a new high oxygen affinity hemoglobin variant found in two families of Finnish origin. Several members representing three generations of two families with erythrocytosis due to a newly described hemoglobinopathy (Hb Linkoping, beta 36 Pro Thr) were studied. All affected family members had a pronounced left-shift of the oxygen dissociation curve, indicating an increased oxygen affinity leading to compensatory erythrocytosis. The proband of each family was found by a simple method determining the oxygen pressure at half hemoglobin saturation (P50), which was used as a screening test evaluating patients with polycythemia. In both cases the hemoglobinopathy was missed by routine hemoglobin electrophoresis. The abnormal hemoglobin was confirmed by isoelectric focusing and the altered amino acid sequence was identified by reversed-phase high-performance liquid chromatography (HPLC). The importance of a correct diagnosis in patients with erythrocytosis due to high-affinity hemoglobin variants is discussed.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
8/9. Hemoglobin Bethesda causing polycythemia in a Japanese family.A family with Hemoglobin Bethesda is reported. A 23-year-old man was hospitalized for the evaluation of polycythemia. Analysis of hemoglobin using high pressure liquid chromatography showed the presence of hemoglobinopathy. Separation of globin into alpha and beta chains revealed approximately 50% of the beta chain to be abnormal. Analysis of the dna sequence of the beta chain gene identified Hb Bethesda. The family study disclosed that his father and sister also had the same hemoglobinopathy. This case is the first report of Hb Bethesda in japan.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
9/9. Hb Puttelange [beta 140(H19)Ala-->Val] in an Italian man with polycythemia.Hb Puttelange [beta 140(H18)Ala-->Val] was found in a 51-year-old Italian man who had mild polycythemia. The variant eluted from ion exchange high performance liquid chromatography at a position between Hb A and Hb A2. It comprised approximately 34% of the total hemoglobin, was weakly unstable and exhibited an increased oxygen affinity. Amplification of the beta-globin exons and nucleotide sequencing revealed a heterozygosity for a GCC-->GTC mutation in codon 140 corresponding to an Ala-->Val replacement. This substitution accounts for the altered functional properties, probably by producing indirect perturbation of the 2 3-diphosphoglycerate pocket through the nearby lysine residue at beta 82(EF6).- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |