Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we used cloning and sequence analysis to define the molecular defect in two delta-thalassemia genes, one associated with reduced output of delta-globin chains (delta +thal) from a Sardinian and the other with a complete suppression of delta-chain production from the affected locus (delta zerp thal) from a Southern Italian. Sequence analysis of the delta +thal gene showed a G----T substitution at the first nucleotide of codon 27 (delta +27) which produces an amino acid change (Ala----Ser) and presumably activates a cryptic splice site located at this position. Therefore, only a fraction of the transcript is processed from this site, as indicated by the clinical phenotype of delta +thal. DNA sequencing of the delta zero thal gene revealed a T----C substitution at position 1 of IVS-1, which abolishes the splicing at this site and thus leads to complete deficiency of normal mRNA explaining the clinical phenotype of delta zero thal. Oligonucleotide analysis was used to confirm the coinheritance of the delta +27 mutation in a group of Sardinians with thalassemia like phenotype and normal HbA2 level who, on the basis of genetic criteria, were supposed to be double heterozygous for delta-thalassemia and beta-thalassemia. The definition of delta-thalassemia defects in each high-risk area facilitates identification of double heterozygotes for delta- and beta-thalassemia by DNA analysis and may thus improve genetic counseling.
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PMID:Delineation of the molecular basis of delta- and normal HbA2 beta-thalassemia. 340 92

Hemoglobin La Desirade is a new unstable hemoglobin variant arising from the substitution of beta 129 (H7) Ala for Val. Hb La Desirade exhibits a low oxygen affinity and normal heme-heme interaction. The variant was found in two unrelated black families in association with Hb S, Hb C or beta o thalassemia.
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PMID:Hemoglobin La Desirade alpha A2 beta 2 129 (H7) Ala----Val: a new unstable hemoglobin. 355 94

Hb Knossos is a beta-chain variant (beta 27 Ser----Ala) that is unrecognizable by conventional separation methods but detectable by globin electrophoresis on urea-Triton X-acrylamide gels or by IEF. Hb Knossos is characterized by reduced synthesis and by interaction with beta-thalassemia, in which the double heterozygotes display typical features of thalassemia intermedia. The present paper summarizes the salient genetic, clinical, and biochemical characteristics of five such cases hitherto identified in three families along with the same features on 12 heterozygous Hb Knossos carriers. Hb Knossos displays a slightly decreased oxygen affinity; this factor may compensate in part for the severe anemia of the double heterozygotes. Hb Knossos is relatively rare in our population, since a prospective survey on 610 individuals has failed to disclose any heterozygotes. However, the mutation appears to have spread over the Mediterranean countries and may be more common elsewhere.
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PMID:Hemoglobin Knossos: a clinical, laboratory, and epidemiological study. 394 30

Hb Knossos (beta 27 (B9) Ala----Ser) is a recently discovered hemoglobin variant endowed with beta-thalassemic properties (1,2) We present the first homozygous cases. The propositus, a 19-year-old man is originally from northeast Algeria, but is unrelated to other Algerians who have hemoglobin Knossos. He has a beta(+)-thalassemia intermedia syndrome, including microcytic, hypochromic anemia, enlargement of the spleen, and an increase in the number of reticulocytes. The reduction of beta-chain synthesis is pronounced (alpha/non alpha:2.76). Whole cells containing Hb Knossos have a dramatically low oxygen affinity (P50:38 mm Hg). The propositus also has homozygous delta(0)-thalassemia. The chromosome carrying these mutations is characterized by the DNA haplotype I.
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PMID:Homozygous hemoglobin Knossos (alpha 2 beta 227(B9) Ala----Ser): a new variety of beta (+)-thalassemia intermedia associated with delta (0)-thalassemia. 395 38

The fetal hemoglobin in the affected members of three Greek families with the hereditary persistence of fetal hemoglobin has only gamma-chains of the type with alanine in position 136. Although certain Negro families had been considered to have only this type of gamma-chains in their fetal hemoglobin, further studies required that they be reclassified. Consequently, the Greek cases are the sole examples of this class among the heterozygotes for the hereditary persistence of fetal hemoglobin. In Greek double heterozygotes for beta-thalassemia and the hereditary persistence of fetal hemoglobin, fetal hemoglobin is increased above the level of hemoglobin F in simple heterozygotes and gamma-chains with glycine in position 136 become apparent. In these individuals, gamma-chains with alanine in position 136 apparently derive from the chromosome for the hereditary persistence of fetal hemoglobin and are present in the hemoglobin F with gamma-chains of both types from the chromosome for beta-thalassemia. When these data are correlated with earlier knowledge of the genetic state of the Greek individuals, modifications of our previous ideas about deletions as the genetic basis of the hereditary persistence of fetal hemoglobin must be considered.
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PMID:Nature of fetal hemoglobin in the Greek type of hereditary persistence of fetal hemoglobin with and without concurrent beta-thalassemia. 544 39

Hb Knossos alpha 2 beta 2 27 Ala----Ser was first described in a Greek family as a silent beta(+) thalassemia variant. Reexamination of 5,000 isoelectric focusing patterns of patients with microcytosis allowed the presumptive identification of two additional propositi. The first originated in the French West Indies (Martinique) and the second in Algeria. A branch of the family of the second propositus was also investigated. Identification of Hb Knossos was made easily in the first family since one member was a double heterozygote for Hb S and Hb Knossos. In the second family HPLC elution of the peptide fragments obtained by tryptic digestion of the aminoethylated beta chain allowed the isolation and characterization of an abnormal beta T3 peak with expected beta 27 Ala----Ser substitution. The Hb Knossos heterozygote from Martinique, besides an elevated alpha/beta globin chain ratio, had an elevated Hb A2 concentration in contrast to the Greek and Algerian families in which it was normal. This difference in phenotypes may be explained by the occurrence in the Mediterranean cases of a delta gene abnormality, presumably delta(0) thalassemia, in position cis to the abnormal beta-globin gene.
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PMID:Two new cases of heterozygosity for hemoglobin Knossos alpha 2 beta 2 27 Ala----Ser detected in the French West Indies and Algeria. 646 98

We report on a 54 years-old male patient from North-Eastern Algeria who combines two hemoglobin variants that are associated with thalassemia-like disorders: Hb Lepore and Knossos (beta 27 Ala----Ser) (1, 2). A beta-thalassemia intermedia picture gradually developed and finally required splenectomy at the age of 53. Total absence of Hb A2 indicated that the beta Knossos gene is most probably flanked with a delta(0)-thalassemia gene. No DNA deletion additional to the Lepore deletion was found. Hb F was elevated (12.3%) with 24% G gamma Hb F. In whole cells, Hb Knossos, representing 70% of total hemoglobin, displayed a decreased affinity for oxygen (P50 = 35 mm Hg), a fact presumably accounting for the relatively good tolerance of the condition.
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PMID:The association of hemoglobin Knossos and hemoglobin Lepore in an Algerian patient. 646 99

The amino acid compositions of tryptic peptides and cyanogen bromide fragments of the purified zeta chain of Hb Portland I (zeta 2 gamma 2) and Hb Portland II (zeta 2 beta 2) have been determined. The hemoglobins were obtained from blood from neonates with hydrops fetalis due to homozygous alpha-thalassemia. The globin chains, tryptic peptides and cyanogen bromide fragments were all separated by reverse phase high performance liquid chromatography (HPLC). Several different types of C-18 columns were used with two different developer systems. The tryptic peptides of aminoethylated zeta chain were separated using an ammonium acetate-acetonitrile gradient. An aqueous trifuoroacetic acid-1-propanol developer gradient was used for the separation of cyanogen bromide fragments. Of the seventeen tryptic peptides obtained, two (zeta T10a and zeta T10b) resulted from the unusual cleavage of a Tyr-Ile peptide bond. This was observed even when using TPCK treated trypsin. From this study and results of others, it can be deduced that trypsin will hydrolyze the Tyr-X bond provided either Ala or Ile is bonded to the N-terminal side of Tyr and Ile, Leu, or Gly is bonded to the C-terminal side of the Tyr residue.
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PMID:Separation of the tryptic peptides and cyanogen bromide fragments of the human embryonic zeta chains of hemoglobin in Portland I and II by reverse phase high performance liquid chromatography. 650 Sep 86

Serum ferritin concentrations have been measured in 124 patients with homozygous beta thalassaemia who were between 2 and 21 years old, had received 11--504 units of blood but had not undergone splenectomy. There were highly significant correlations between serum ferritin concentration and both the amount of blood transfused and alanine amino-transferase (ALT) activity. However, multivariate analysis showed that units of blood and ALT activity together only accounted for about 30% of the variation in serum ferritin concentration. Little of the remaining variation could be explained by other variables related to iron metabolism or liver damage. The concentration of concanavalin A binding ferritin increased rapidly with the number of units of blood up to 100 units but thereafter showed no further increase with number of transfusions. The concentration of non-binding ferritin was more closely related to transfusion load. These results suggest that the secretion of glycosylated ferritin from reticuloendothelial cells reaches a maximum with increasing iron accumulation, perhaps reflecting a maximum rate of synthesis. Ferritinaemia in patients with transfusional iron overload therefore seems to be the result of the combined effects of increased ferritin synthesis and the release of intracellular ferritin from damaged cells. A simple relationship between serum ferritin and iron stores cannot be assumed when ferritin concentrations exceed 4000 microgram/l or in patients who have received more than 100 units of transfused blood.
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PMID:Binding of serum ferritin to concanavalin A: patients with homozygous beta thalassaemia and transfusional iron overload. 744 26

A 67-year-old woman with pulmonary embolism was suspected to have beta-thalassemia based on microcytosis, hemolysis and a negative red cell stability test. The DNA sequencing analysis of beta-globin gene, however, revealed the deletion of three nucleotides within codon 127-128, leading to substitution of glutamine and alanine residues at 127 and 128 by proline, namely Hb Gunma. This mutant is characterized by the fact that no abnormal hemoglobin is detected in the circulating blood, and is classified as a thalassemic hemoglobinopathy. The present case showed a relatively hemolytic manifestation.
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PMID:Hb Gunma (beta Gunma) with pulmonary embolism. 764 5


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