1/15. The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma -thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family.The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma -thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma -thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma -thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma -thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma -thalassemia is responsible for neonatal hemolytic anemia in this family.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/15. prenatal diagnosis of heterozygous beta-thalassemia.The parents of a child with homozygous thalassemia of the beta O variety requested prenatal diagnosis during a subsequent pregnancy. At the 19th week of pregnancy, a sample of blood containing fetal cells was obtained by placentocentesis. Radiochromatography of globin chains demonstrated production of a beta-chain with a beta/gamma synthetic ratio of 0.049, which is low for this gestational age. The conclusion that the child would be heterozygous for the beta-thalassemia gene was confirmed after birth.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/15. beta-thalassemia intermedia caused by compound heterozygosity for Hb Malay (beta codon 19 AAC-->AGC; asn-->Ser) and codons 41/42 (-CTTT) beta(0)-thalassemia mutation.We report a case of beta-thalassemia intermedia caused by compound heterozygosity for hemoglobin (Hb) Malay and codon 41/42 (-CTTT) beta(0)-thalassemia mutation in a 38-year-old Chinese woman. This patient has long-standing anemia with a baseline Hb level of around 70 g/L. She worked as a full-time cashier and had not required regular blood transfusions. Nevertheless, she had splenomegaly necessitating splenectomy, cholelithiasis, and iron overload. This case illustrates the varied phenotypic expression associated with compound heterozygosity for Hb Malay and other beta-thalassemia mutations. Since Hb Malay migrates as Hb A on electrophoresis and chromatography, this variant Hb mutation ought to be included in the differential diagnosis for beta-thalassemia major or intermedia patients of Southeast Asian descent who are reported to have Hb A on the basis of Hb analysis. The possible presence of this mutation should also be considered in appropriate cases for genetic counseling in couples at risk of conceiving fetuses with beta-thalassemia major or intermedia.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/15. Hb Leslie, an unstable hemoglobin due to deletion of glutaminyl residue beta 131 (H9) occurring in association with beta0-thalassemia, HbC, and HbS.A new unstable hemoglobin, Hb Leslie, has been observed in three generations of a georgia family. The propositus, a 42-yr-old black veteran with hemolytic anemia and splenomegaly, has a hemoglobin variant with an electrophoretic mobility similar to that of hemoglobin F. The variant comprises about 85% of the total hemoglobin and was isolated by chromatography. Chemical analysis has identified the abnormality as a deletion of the glutaminyl residue in position 131 (H9) of the beta-chain. Deletion of this critical residue which participates in the alpha1beta1 contact causes decreased stability of the hemoglobin without significant changes in functional properties or morphologic abnormalities in the erythrocyte. family studies revealed hemoglobin Leslie occurring in combination with beta0-thalassemia, HbS, and HbC. All persons with the various Hb Leslie combinations, including the propositus, have no clinical manifestations other than anemia. In some the anemia is fully compensated. There is no history of drug-associated hemolysis.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/15. Differential diagnosis of adult hemoglobin a, F, and S conditions. A case of G gamma-beta( )-hereditary persistence of fetal hemoglobin.Hemoglobin (Hb) S/beta( )-thalassemia is a hemoglobinopathy of variable but potentially severe clinical course. The condition is usually confirmed by the presence of a microcytic anemia and elevated levels of Hbs S, F, and A2 by electrophoresis. However, other less common disorders of Hb structure and synthesis may exhibit laboratory findings that mimic Hb S/beta( )-thalassemia but have a more favorable prognosis. We present a case occurring in a man with clinical and laboratory features that were suggestive of Hb S/beta( )-thalassemia but with normocythemia. Although nonmicrocytic variants of beta( )-thalassemia, including concomitant nutritional deficiencies, were considered, high-pressure liquid chromatography revealed nearly all of the patient's fetal Hb to contain only G gamma chains. This pattern is most consistent with the rate but clinically benign condition of Hb S/G gamma-beta( )-hereditary persistence of fetal Hb, a nondeletional type of hereditary persistence of fetal Hb. We discuss a diagnostic approach to adult Hb A, F, and S conditions, including thalassemias and thalassemia-like syndromes.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/15. A single nucleotide deletion in codon 123 of the beta-globin gene causes an inclusion body beta-thalassaemia trait: a novel elongated globin chain beta Makabe.The beta-globin gene from a Japanese individual with an inclusion body beta-thalassaemia trait has been characterized by gene cloning and dna sequencing. An adenine deletion was detected at the first position of codon 123 (ACCCC) of one allele whereas the other allele had a normal sequence. Heterozygosity for this mutation in the patient was confirmed by Southern blots of the genomic dna digested with HphI, the recognition site of which is eliminated by this deletion. This one base deletion results in the shift of a reading frame in such a manner that the normal termination codon is out of phase. This frameshift mutation results in the synthesis of an elongated beta-globin chain with 10 extra amino acid residues and with an altered C-terminus. Analysis of labelled globin chains using CM-cellulose column chromatography failed to demonstrate any abnormal protein, thereby suggesting that the beta-globin chain variant is highly unstable and probably degrades rapidly after synthesis. This event will lead to an accumulation of free alpha-chains precipitating in the red blood cells and an inclusion body beta-thalassaemia phenotype would ensue.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
7/15. beta-thalassemia intermedia in two Turkish families is caused by the interaction of Hb Knossos [beta 27(B9)AlaSer] and of Hb City of hope [beta 69(E13)Gly ser] with beta (0)-thalassemia. We have studied a few members of two Turkish families, who had a beta-thalassemia of the intermediate type. An abnormal hemoglobin was found in both families, which when present in association with beta(0)-thalassemia was considered to be the primary cause for the increased severity of the disease. In the first family this variant was Hb Knossos [beta 27(B9)Ala Ser] which occurred together with the frameshift in codon #8 type of beta(0)-thalassemia. This compound heterozygosity, observed for the first time in the Turkish population was characterized by a considerable increase in Hb F production, mainly of the G gamma type, as expected for a chromosome with haplotype IV. In the second family, the variant was Hb City of hope [beta 69(E13)Gly Ser] which was present in combination with an unknown type of beta-thalassemia. The increase in Hb F production in the compound heterozygote was minimal. Reversed phase high performance liquid chromatography and the dna amplification-synthetic oligonucleotide probe procedure were major tools in identifying the different abnormalities.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
8/15. hemoglobin j Guantanamo [alpha 2 beta 2 128 (H6) AlaAsp] in association with hemoglobin c and alpha-thalassemia in a family from benin. hemoglobin j (HbJ), Guantanamo, which had been described but once in the literature, was found in a family originating from benin; this second case was found to be in association with hemoglobin c (HbC) and alpha-thalassemia. High-performance liquid chromatography (HPLC) procedures and microsequencing were used for characterization of the aminoacid substitution. The main hematological disorder, in relation with the instability of Hb J Guantanamo, seems to be a worsening of the rheological properties of the red blood cells (RBC), as demonstrated by ektacytometric studies. oxygen-binding properties of the RBC were almost normal, but a slight decrease in cooperativity and lowered Bohr and 2,3-diphosphoglycerate (DPG) effects were observed for pure stripped Hb J Guantanamo. The expression of the electrophoretic charge difference was partly masked, as is often observed when the structural abnormality is situated in or near a contact area.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
9/15. HB Q-thailand-HB H disease in a Chinese living in Geneva, switzerland: characterization of the variant and identification of the two alpha-thalassemic chromosomes.Data on a 24-year-old Chinese male with Hb Q-thailand-Hb H disease are presented. The hemoglobin variant was characterized by fast microprocedures, mainly by reverse-phase high-performance liquid chromatography. Gene mapping analyses identified the alpha-thalassemia-2, which is associated with the alpha-Q chain, as caused by a 4.2-kb deletion involving the alpha 2 globin gene, while the alpha-thalassemia-1 anomaly was the common Southeast Asian type in which part of the psi zeta, the psi alpha, and the alpha 2 and alpha 1 globin genes are deleted.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/15. Hemoglobin Hofu associated with beta 0-thalassemia.A mild anemia (hemoglobin 9 g/dl) was found in a patient from Seville (spain) with marked morphological abnormalities in the peripheral blood smear. The red cell osmotic fragility showed a mild resistance curve with a mean cell fragility (MCF) of 0.375% NaCl (normal = 0.450). Chemical Chemical and thermal instability test and search for inclusion bodies gave positive results. Hemoglobin electrophoresis at pH 8.9 revealed absence of Hb A, a major component of fast mobility (94%), and increased Hb F and Hb A2 levels (1.5% and 4.6%, respectively). The fast fraction, isolated and purified by means of cellulose acetate electrophoresis, precipitated in acid acetone and treated with urea 8 M and mercaptoethanol, revealed an anomalous beta chain. trypsin-digested globin peptides were separated by high-voltage electrophoresis at pH 6.4 and ascendant chromatography. With differential staining, an extra peptide was detected in an unusual site, more anodic than alpha Tp4 but in lower position. Peptide map of the fast beta chain, stained with ninhydrin, and also for Tyr, confirmed the position of the new peptide and the absence of the usual beta Tp13. The new peptide, separated by high-voltage electrophoresis at pH 3.5, revealed absence of Val and the presence of an additional Glu residue, which should appear only in position beta 126. The diagnosis of Hb Hofu (alpha 2 beta 2 126 Val Glu; H4) was reached, thus interpreting its increase and the absence of Hb A, as an association with beta o-thalassemia, producing a mild hemolytic anemia. Evidence was obtained that Hb Hofu is a mild unstable hemoglobin variant.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
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