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)

The ratio of Ggamma to Agamma was studied in 13 normal healthy newborns and in eight neonates with hydrops fetalis due to homozygous alpha-thalassemia. The findings in the normal healthy newborns agreed with those of earlier reports. In homozygous alpha-thalassemia the Ggamma and Agamma ratio appeared generally lower than in healthy control newborns, but one of the hydrops fetalis cases had a very high Ggamma value. In all 13 normal healthy newborns, in 8 patients with homozygous alpha-thalassemia, and in 4 patients with homozygous beta-thalassemia, Tgamma chains with threonine at position 75 were detected in addition Igamma chains with isoleucine at position 75. In homozygous alpha-thalassemia, the Tgamma-to-Igamma ratio seemed lower and in homozygous beta-thalassemia higher than in normal newborns.
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PMID:Heterogeneity of hemoglobin gamma chains in normal newborns and in cases of alpha and beta thalassemia. 45 94

The hematological phenotypes of several Mediterranean patients with delta beta-thalassemia and hereditary persistence of fetal hemoglobin have been characterized. Although clinical and hematological characteristics are essentially superimposable in all heterozygous delta beta-thalassemics, these patients show typical G gamma/A gamma ratios in their Hb F, ranging from approximately 0.07 in Sardinian to approximately 0.15 in Sicilian and approximately 0.35 in Spanish patients. A gamma Sardinian-(isoleucine-75 leads to threonine) is found in Spanish patients and accounts for all of the A gamma production in heterozygotes, indicating that persistent production of gamma chains occurs cis to the delta beta-thalassemia gene. The molecular heterogeneity of these conditions is demonstrated by restriction enzyme mapping of DNA; Sicilian and Calabrian patients show a deletion starting from the delta-globin intron and extending several kilobases 3' to the beta-globin gene; in Spanish patients the deletion starts approximately 2-3 kilobases 5' to the delta-globin gene and extends well beyond the beta-globin gene. Comparison of these deletions with previously described ones in Negro and in a new Southern Italian case of hereditary persistence of fetal hemoglobin suggests that the deletion of a region centered at a cluster of repetitive sequences approximately 3.5 kilobases 5' to the delta-globin gene may be critical for the persistent expression of high levels of gamma-globin in hereditary persistence of fetal hemoglobin compared to delta beta-thalassemia. The concept that the deletion or mutation of specific areas (rather than nonspecific changes brought about by large deletions in the globin cluster) is important in determining the persistent expression of gamma-globin genes is supported by the finding of a nondeletion type of delta beta-thalassemia in Sardinians.
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PMID:Molecular comparison of delta beta-thalassemia and hereditary persistence of fetal hemoglobin DNAs: evidence of a regulatory area? 617 97

In beta zero-thalassemia and sickle cell patients, a 4 bp deletion at -222 to -225 of the A gamma globin promoter was associated with low expression of the A gamma T variant (threonine at codon 75 of A gamma), whereas A gamma I (isoleucine at 75) had the normal A gamma promoter and higher expression. However, it has been reported that the beta A chromosomes of sickle cell trait cases have the 4 bp deletion as a common polymorphism unlinked to the A gamma T allele. We now present data demonstrating the association of the A gamma T allele with the 4 bp deletion in beta A chromosomes of sickle cell traits.
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PMID:Direct demonstration that the A gamma T globin gene is linked to the 4 bp promoter deletion in the beta A chromosome of sickle cell traits. 837 15

We have characterized a new abnormal hemoglobin (Hb) at position 32 of the alpha-globin chain. The proband, a 38-year-old woman of Surinamese Black ancestry, was referred to the Academic Hospital in Amsterdam, The Netherlands, after 3 years of Prednisone treatment in Surinam. Kidney failure was diagnosed at the Nephrology Department, Free University Medical Center, Amsterdam, The Netherlands; the cortisone treatment was interrupted and dialysis was started. At this stage, a microcytic hypochromic anemia was observed with high reticulocyte (40%) and ferritin (500 microg/L) levels, and hemoglobinopathy was suspected. No abnormal bands were visible on alkaline electrophoresis and high performance liquid chromatography (HPLC). The Hb A2 level was normal (2.7%) and the erythrocyte count was low (3.59 x 10(12)/L) with a normal haptoglobin level (68 mg/100 mL). None of the common alpha-thalassemia (thal) deletion defects were present. The beta-globin gene sequence was normal but the alpha2-globin gene sequence revealed an ATG-->ATA transition at codon 32, changing the methionine into an isoleucine residue. The mutation, called Hb Amsterdam, was observed in the mother of the proband, who was also heterozygous for the--alpha3.7-thal deletion and affected by a moderate microcytic hypochromic anemia. Both Hb Amsterdam and the--alpha(-3.7) allele were found in association with a new polymorphism, IVS-I-39 (C-->T), previously observed in our laboratory in seven patients of African origin, on both the alpha1 and alpha2 genes. In addition, Hb Amsterdam was also associated with the common African alpha2 polymorphism (G-->CTCGGCCC at position 7238 and T-->G at position 7174). Hb Amsterdam is the first mutation ever described at codon alpha32, a position involved in alpha1/beta1 interaction. The possibility of a contribution of this mutation to the nephropatic state of the proband is discussed.
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PMID:Hb Amsterdam [alpha32(B13)Met--Ile (alpha2)]: a new unstable variant associated with an alpha-thalassemia phenotype and a new African polymorphism. 1637 Apr 85

Alpha-hemoglobin stabilizing protein (AHSP) is a potential modifier of beta-thalassemia by virtue of its ability to detoxify excess free alpha-globin. However, examination of patients with beta-thalassemia from a few geographic regions failed to identify obvious AHSP mutations. We extended these studies by analyzing AHSP gene sequences in 366 anonymous individuals from five different areas of the world. We detected numerous polymorphisms comprising 18 different haplotypes and two rare missense mutations. Two sequence variations produce functional effects in laboratory assays. First, a rare missense mutation in a Brazilian/Mediterranean cohort converts asparagine to isoleucine at position 75 of AHSP protein and impairs its ability to inhibit reactive oxygen species production by alpha-hemoglobin. Second, a high-frequency polymorphism in intron 1 of the AHSP gene (12391 G>A) alters an Oct-1 transcription factor binding site previously shown to be important for optimal gene expression. The 12391A polymorphism impairs Oct-1 binding and inhibits the ability of AHSP regulatory sequences to activate expression of a linked luciferase reporter. Although structural mutations predicted to alter AHSP protein function or ablate its activity are rare, the 12391 G>A SNP is common and represents a potential mechanism through which genetically determined variations in AHSP expression could influence beta-thalassemia.
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PMID:Population analysis of the alpha hemoglobin stabilizing protein (AHSP) gene identifies sequence variants that alter expression and function. 1787 50