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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of fetal hemoglobin was investigated in in vitro cultures of erythroid precursors isolated from peripheral blood of normal individuals, newborns and of subjects with different hemoglobinopathies. Synthesis of hemoglobin was assessed by 35s-methionine labeling of cultures and measurement of the radioactivity incorporated into the hemoglobins A2, A, F and S isolated by column chromatography on DE 52 cellulose. The erythroid precursors from most of the studied individuals cultured in in vitro system responded with synthesized an average of 15% of Hb F while cultures from newborns produced an average of 60% of Hb F in comparison of 73% of Hb F in peripheral blood of the same newborns. Erythroid precusors from subjects heterozygotes for beta-thalassemia, heterozygotes for HPFH, and homozygotes for Hb S produced an average of 20%, 43% and 30% of Hb F, respectively, in comparison of 7%, 14% and 9% of Hb F, respectively, present in the RBC of the same individuals. These data support the previously published results (6-11) that erythroid bursts in culture reactivate the structural genes for the gamma chain synthesis.
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PMID:[Preferential synthesis of fetal hemoglobin in in vitro cultures of erythroid precursors from peripheral blood of healthy persons and those with hemoglobinopathies]. 9 30

The biosynthesis of two types of human fetal hemoglobin (Hb F), namely Hb F with G gamma chains having glycine in position 136 and Hb F with A gamma chains having alanine in position 136, was studied in blood samples and in cultures of erythroid precursors from blood of patients with different hemoglobinopathies. High pressure liquid chromatography (HPLC) was adapted to allow the separation of the methionyl-containing tryptic peptides G gamma T-15 and A gamma T-15 (which include the Gly leads to Ala polymorphism at position 136) from a digest of microquantitites of 35S-methionyl labelled Hb F. This method was sensitive enough to quantitate the relative production of the G ygamma and A gamma chains by erythroid colonies derived from cloned Burst Forming Units (bfu-e) which were cultured for 16 days on methylcellulose. The production of Hb F in these colonies was generally higher than the level of Hb F in blood except for subjects with the G gamma A gamma-HPFH heterozygosity. The G gamma to A gamma ratio in the Nb F produced in cultures of cells from G gamma delta beta-thalassemia or G gamma-HPFH heterozygotes was lower and that from A gamma-HPFH heterosygotes was higher than the ratios in the Hb F of the corresponding peripheral blood cells. Mixtures of G gamma and A gamma chains were present in cell cultures of SS patients, beta+-thalassemia homozygotes and G gamma A gamma-HPFH heterozygotes in a ratio similar to that in the Hb F of mature red cells. These data suggest that erythroblasts in BFU-E derived colonies reactivate all available gamma chain structural genes, both in cis and in trans to the abnormal determinant. Hb F biosynthesis by adult blood samples concerns primarily the G gamma chains. This was particularly striking for blood samples in which erythroblasts were absent and the biosynthesis took place in fetal reticulocytes. Thus, the F-retuculocytes in blood of A gamma-HPFH heterozygotes with about 5% Hb F of the A gamma type produced primarily Hb F with G gamma chains. Similar differences were observed for G gamma A gamma-HPFH heterozygotes and, less strinkingly, for SS patients. A satisfactory explanation for this observation has not yet been obtained.
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PMID:The synthesis of fetal hemoglobin types in red blood cells and in BFU-E derived colonies from peripheral blood of patients with sickle cell anemia, beta+ - and delta beta-thalassemia, various forms of hereditary persistence of fetal hemoglobin, normal adults and newborn. 50 Mar 69

High levels of HbF were found in patients with myelodysplastic syndrome (MDS), as well as a possible switching of the ratio of the gamma chains from the adult to the newborn type in 25% of our patients. These abnormalities in general were not present in the parents. The possibility of having thalassemia or other hemoglobinopathies was excluded. The fetal hemoglobin percentage was quantitated by alkali denaturation of the hemolysate, and the gamma chain content was determined in blood hemolysate by HPLC following HbF isolation. A 7/3 ratio of fetal Gy/Ay was found in three patients. Since the survival of MDS patients with high HbF levels was longer than that of patients with low levels of HbF, this finding may be used as a potential prognostic factor.
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PMID:Quantitation of HBF gamma-chain types by HPLC in patients with myelodysplastic syndrome. 172 40

In the course of our newborn screening program for the presence of hemoglobinopathies in the Republic of Macedonia, we have detected a new G gamma chain variant with a Lys-->Asn or AAG-->AAC substitution at codon 104. The variant was found in a blood sample from a healthy baby boy of Macedonian nationality. The abnormal chain was quantitated at 32.4% of the total gamma chains by reversed phase high performance liquid chromatography. The characterization of the variant was by sequence analysis of polymerase chain reaction-amplified DNA. The presence of the mutation in the mother was confirmed by Hph I restriction enzyme digestion of the polymerase chain reaction-amplified DNA fragment. Although the mutated G is the last nucleotide of exon 2 and part of the donor splice site sequence of the second intervening sequence of the G gamma gene, it appears that the splicing of the mRNA in this variant is not altered.
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PMID:Hb F-Macedonia-II [G gamma 104(G6)Lys-->Asn]: a new gamma chain variant. 771 41

Hemoglobin (Hb) F-Mauritius, a new A gamma chain variant, was identified from a dried blood spot collected from a heelprick during neonatal screening for the main hemoglobinopathies. This hemoglobin is the first gamma chain variant having a one residue deletion: it concerns alanine at position gamma 23. Hb F-Mauritius is therefore the counterpart of Hb Freiburg, an unstable variant of the beta chain in which the valine residue that occupies position beta 23 is deleted. The structural modification of Hb F-Mauritius was characterized by miniaturized protein chemistry methods, including sequence determination by mass spectrometry measurements. Hb Freiburg was used as a control in several experimental procedures. The hypothesis that a similar mechanism for deletion has occurred in Hb F-Mauritius and in Hb Freiburg is supported by the high percentage of homology observed between the beta and gamma globin genes. In addition, the first exon of the beta-globin has been recognized as a hotspot for deletion: several beta-thalassemic mutations, or abnormal Hbs, with deletions of short nucleotide sequences map in this region.
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PMID:Hb F-Mauritius [A gamma 23 (B5) Ala deleted]: evidence for an identical hotspot for deletions in the various beta-like genes. 855 53

Quantitation of fetal hemoglobin (Hb F) and quantitation of it's gamma chain composition is important for the identification of different hemoglobinopathies. This is the first study done on the Jordanian newborns to test the hematological data and the gamma globin chain variants. A total of 52 randomly selected healthy Jordanian newborns were examined. The quantitation of the G gamma and A gamma chains combined with gene mapping using XmnI digestion, were used in the identification of one case of G gamma triplication among the studied samples. A family study of this case showed that adults carrying one copy of this G gamma triplication (13Kb XmnI fragment) had normal levels of HbF (< 1%) and high levels of G gamma (> 80%) while no homozygotes were detected. The remaining 51 newborns had normal frequency values of G gamma and A gamma chains. The frequency of the A gamma T chain among the 52 samples was 0.22. No abnormal alpha or beta chain variants were detected except for one case of HbS.
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PMID:Studies on fetal hemoglobin and gamma globin gene triplication in newborns in Jordan. 977 99

This paper summarizes the results on the epidemiology and molecular basis of thalassemias and other hemoglobinopathies in the Republic of Macedonia. Over the past 40 years, population surveys of more than 22,000 participants (school children and workers) from all over the country, have shown that the average incidence of beta-thalassemia (thal) trait is 2.6%, ranging from less than 1% in the northeast to 10% in the south. The frequency of deltabeta-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.3%. Screening of 9,619 newborns has shown that the frequency of alpha-thal trait is 1.5%, of which alpha-thal-2 is 1.45% and alpha-thal-1 is 0.05%. The molecular basis of the different forms of beta-thal and other hemoglobinopathies has been completely defined. Among the Macedonians, over 450 beta-thal chromosomes have been studied. Fifteen different beta-thal mutations have been detected, four of which [IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-I-1 (G-->A), codon 39 (C-->T)] account for 85% of all beta-thal chromosomes. Among the Albanians, 48 beta-thal chromosomes have been studied. Eight different mutations have been detected, four of which [codon 39, -30 (T-->A), IVS-I-110, IVS-I-1] account for 85% of all beta-thal chromosomes. Four new mutations [-101 (C-->A), -87 (C-->G), -30, polyadenylation signal (poly A) (AATAAA-->AATGAA)] have been characterized. Molecular analyses of DNA from over 20 unrelated cases with deltabeta-thal have shown that this condition is caused by a 13 kb deletion (Sicilian type); in two families a deletion of 18 to 23 kb (Macedonian type of deltabeta-thal) was discovered. Molecular analyses of alpha-thal in the Republic of Macedonia have shown the following types of molecular defects: 20.5 kb deletion, 17.5 kb deletion, 3.7 kb deletion, poly A mutation (AATAAA-->AATGAA), and Hb Icaria [alpha142, Term-->Lys, TAA-->AAA (alpha2)]. The incidence of abnormal hemoglobins (Hbs) in the Republic of Macedonia is 0.4%. Three different alpha chain variants among 10 families, seven different beta chain variants among 33 families, two gamma chain variants in two newborns, one variant with an extended alpha chain, and Hb Lepore among 105 families, have been observed. Structural analysis of numerous cases with Hb Lepore showed that the variant was of the Washington-Boston type.
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PMID:Thalassemias and other hemoglobinopathies in the Republic of Macedonia. 1736

Fetal hemoglobin (HbF), the predominant hemoglobin in the fetus, is a mixture of two molecular species (alpha(2)(G)gamma(2) and alpha(2)(A)gamma(2)) that differ only at position 136 reflecting the products of two nonallelic gamma-globin genes. At the time of birth, HbF accounts for approximately 70% of the total Hb. The (G)gamma:(A)gamma globin ratio in the HbF of normal newborn is 70:30 whereas in the trace amounts of HbF that is found in the adult it reverses to 40:60 because of a gamma- to beta-globin gene switch. Alterations of these ratios are indicative of a molecular defect at the level of the HbF synthesis. Qualitative hemoglobinopathies due to (G)gamma and (A)gamma chain structural variants, and quantitative hemoglobinopathies affecting the synthesis of HbF such as gamma-thalassemias, duplications, triplications, and even sextuplications of the gamma-globin genes, which may be detected in newborn blood lysates, have been described. Moreover, several pathological and nonpathological conditions affecting the beta-globin gene cluster, such as beta-thalassemia, sickle cell disease, deltabeta-thalassemia, and hereditary persistence of HbF syndromes, are characterized by the continued synthesis of gamma-globin chains in the adult life. Studies of these natural mutants associated with increased synthesis of HbF in adult life have provided considerable insight into the understanding of the control of globin gene expression and Hb switching.
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PMID:Disorders of the synthesis of human fetal hemoglobin. 1837 99

Two new fetal hemoglobin (Hb F) variants affecting the (G)gamma chain are reported: Hb F-Saint-Etienne [G gamma 79(EF3)Asp-->His] and Hb F-Lyon [G gamma 97(FG4)His-->Arg]. These new Hb variants were found during a neonatal screening for hemoglobinopathies but characterized a few months later by our reference laboratory. The corresponding mutations are located on the external part of the Hb molecule and seem to be clinically silent.
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PMID:Two new G gamma chain variants: Hb F-Saint-Etienne [G gamma 79(EF3)Asp-->His] and Hb F-Lyon [G gamma 97(FG4)His-->Arg]. 1893 75

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.
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PMID:Two abnormal fetal hemoglobins found in the Sardinian population: the new Hb F-Osilo [(A)gamma119(GH2)Gly-->Ser, GGC > AGC] and Hb F-Paulinia [(G)gamma80(EF4)Asp-->Tyr, GAT > TAT] already described in the Brazilian population. 1995 93


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