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

Reversed-phase high-performance liquid chromatography (RP-HPLC) using the large-pore Vydac C4 column has been used to detect and quantitate the embryonic zeta chain in blood samples of normal babies and of newborns with varying degrees of alpha chain deficiencies. The zeta chain eluted at the end of the chromatogram at about 130 min using a modified and extended gradient. Its identity was confirmed by structural analysis of zeta chain isolated from a blood sample of a fetus without active alpha globin genes, i.e. with hydrops fetalis (--/--). The quantity of zeta in normal babies is less than 0.7% [% of (alpha + zeta)] and is dependent upon the maturity of the baby as it was only present in babies with low levels of beta chain or hemoglobin (Hb) A. The presence of a zeta globin gene deletion [A. E. Felice et al., Hum. Genet., 73 (1986) 221; and P. Winichagoon et al., Nucleic Acids Res., 10 (1982) 5853] did not affect the level of zeta in the newborn. All babies with an alpha-thalassemia-2 heterozygosity, i.e. with three active alpha globin genes or -alpha/alpha alpha, had zeta in a range of 0.1-0.9%; again the level showed a negative correlation with that of the beta chain. Newborns with an alpha-thalassemia-2 homozygosity or -alpha/-alpha had a varying level of zeta of 0.3-2.3%, which did not correlate with the level of beta, suggesting that zeta chain production persists after birth in this condition. Macrochromatographic analyses in combination with RP-HPLC indicated that the zeta chain is present as zeta 2 gamma 2 or Hb Portland-I, as expected.
 ...
PMID:Detection of the embryonic zeta chain in blood from newborn babies by reversed-phase high-performance liquid chromatography. 244 82

The haemoglobinopathies are a group of autosomal recessively inherited diseases that are common among populations in the Mediterranean, in Africa and large parts of Asia. In Germany, the immigration of people from those parts of the world has resulted in an increased occurrence in particular of beta thalassaemia. Homozygous patients usually become transfusion dependent during the first year of life as the excess of alpha globin chains in the erythroid precursors causes a most severe dyserythropoietic anaemia. Genetic determinants that diminish the alpha globin chain excess are thus clinically significant. Here, we describe the molecular genetic changes that result in an increased gamma globin gene expression and hende in a binding of alpha globin chains as HbF. We discuss the significance of those changes for the clinical course of beta thalassaemia and for the elucidation of the ontogenetic processes of gene regulation during the perinatal haemoglobin switch.
 ...
PMID:[The molecular basis of hereditary persistence of fetal hemoglobin (HPFH). Clinical importance of the hemoglobin switching mechanism with special reference to Corfu delta beta zero thalassemia]. 246 59

Twelve members of a Maori family were investigated for alpha-thalassaemia after a provisional diagnosis of thalassaemia had been made on the basis of chronic hypochromic microcytic red cell indices. Ten family members were shown to have the 3.7 kb deletion form of alpha-thalassaemia; two of these were homozygous for this deletion (-alpha/-alpha); eight had the single deletion (-alpha/alpha alpha). While anaemia was not a significant finding, the degree of hypochromicity and microcytosis correlated well with the alpha globin gene status of individual family members. This and other studies provide evidence that alpha-thalassaemia is a significant contributor to the chronic mild anaemia of the Maori.
 ...
PMID:Alpha thalassaemia in the Maori: a family study. 247 Nov 23

In this study, we have defined the beta thalassemia mutation and characterized the beta globin haplotype and the alpha globin gene arrangement in a group of patients of Sicilian descent with beta (s)/beta thalassemia. We found that those patients carrying a beta(+) thalassemia mutation associated with a moderate reduction of beta chain synthesis (beta(+) IVS-1 nt 6) have normal or reduced Hb levels and mild to moderate clinical manifestations, as defined by the number of hospital admission and sickle cell crises per year. Those patients carrying a beta(+) thalassemia mutation associated with a severe reduction of beta chain synthesis (beta(+) IVS-1 nt 110) have a disease of moderate severity. In those carrying a beta(0) thalassemia gene the disease was clinically very heterogeneous, ranging in severity from mild to severe with no difference related to the type of mutation [beta(0) 39, beta(0) IVS-1 nt 1, beta(0) IVS-2 nt 1, beta(0) 6 (-1bp)]. In this last group of patients part of the clinical variability may be attributed to the HbF levels, which were higher in those with mild to moderate clinical severity.
 ...
PMID:The effect of the beta thalassemia mutation on the clinical severity of the sickle beta thalassemia syndrome. 250 7

Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+)-thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I.
 ...
PMID:beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis. 258 95

Alpha-globin genes were analyzed by the direct method of DNA mapping using alpha- and zeta-globin specific probes in a Thai family in which the proposita was an unusually mild beta zero-thalassemia homozygote. alpha zero-Thalassemia was found to be segregating in the family, inherited from the proposita's father by one of her younger sisters. However, alpha zero-thalassemia was not detected by this DNA mapping in the proposita. The mild homozygous beta zero-thalassemia in this family may result from interactions of a non-deletion alpha-thalassemia, a gene responsible for high proteolytic activity permitting more balanced globin-chain levels, or from an unusually active hemoglobin F production in the proposita.
 ...
PMID:Alpha zero- and beta zero-thalassemia in a Thai family: unusually mild homozygous beta zero-thalassemia without alpha-globin gene deletion. 258 Jul 74

Alpha zero-thalassaemia of the British type is described for the first time in a New Zealand family. Microcytic, hypochromic red blood cells were found in affected individuals. Exclusion of iron deficiency and beta-thalassaemia suggested alpha-thalassaemia as a possible cause. This was confirmed by the detection of haemoglobin (Hb) H inclusion bodies. Definitive characterisation of the alpha-thalassaemia defect required DNA mapping which demonstrated the British alpha zero-thalassaemia deletion involving both alpha globin genes. alpha zero-thalassaemia should no longer be considered a disorder affecting individuals of Mediterranean or Asian backgrounds. Anglo-Saxons are also an at risk group. Co-inheritance of this abnormality with a second alpha-thalassaemia defect can lead to Hb H disease or Hb Bart's hydrops fetalis.
 ...
PMID:British type alpha 0-thalassaemia in New Zealand. 273 65

In this paper, we present data on studies of beta S-haplotypes and alpha-thalassemia gene in subjects from the indigenous population of the Coast Province of Kenya Of the 7SS patients studied, four were homozygous for beta S-haplotype 20 characteristically associated with the severe form of sickle cell anemia found in the Central African Republic and Western Kenya. Two had haplotype 20 combined with haplotype 19 (Benin Type) and one had haplotype 20 combined with a new haplotype (20x). Alpha thalassaemia-2 gene (-3.7kb deletion) was detected in 45.6% of the 57AA subjects studied. An alpha globin gene triplication was detected in one subject whereas eight had gamma globin gene triplication.
 ...
PMID:beta S-haplotypes and alpha-thalassemia along the coastal belt of Kenya. 279 41

The effect of isonicotinic acid hydrazide (INH), a potent haem inhibitor, on globin chain synthesis was studied in reticulocytes from the following groups of patients: four non-thalassaemic patients (group i); five beta thalassaemia heterozygotes (group ii); three Hb S/beta thalassaemia heterozygotes (group iii); and two additional patients--one with homozygous beta thalassaemia and the other with thalassaemia intermedia (group iv). This was done to determine whether haem inhibitors depress alpha globin chain synthesis. The progressive increase of INH concentration (10-40 mmol l-1) in reticulocytes from a beta thalassaemia heterozygote resulted in a remarkable decrease of the alpha and beta chain synthesis, ranging from 80% to 97% and from 74% to 96% of control values, respectively, and in a gradual drop of alpha:beta ratio from 1.87 to 1.38. Furthermore, in the samples incubated with 40 mmol l-1 INH, a pronounced inhibition of globin chain synthesis 77 (19%) for alpha chain and 67 (27%) for beta or beta S chain) and a substantial drop of the alpha:beta or beta S ratio in samples with INH (median 1.16) compared with that in samples without INH (median 1.70) were observed. The inhibitory effect of INH was significantly or completely corrected by adding exogenous haem. It is suggested that haem inhibition and the resulting preferential diminution of alpha chain synthesis could provide a new approach to the treatment of homozygous beta thalassaemia with an excess of detrimental free alpha chain in erythroid cells.
 ...
PMID:Effect of isoniazid, a haem inhibitor, on globin chain synthesis in reticulocytes from non-thalassaemic and beta thalassaemic subjects. 279 87

We have examined the alpha globin gene complex for 49 individuals with alpha-thalassemia-2 (-alpha 3.7). Crossovers resulting in alpha-thalassemia-2 (type I) were observed in all 57 chromosomes with the -alpha 3.7 defect. Except for one alpha-thalassemia-2 chromosome, all were linked to the absence of an Rsa I restriction site located 0.7 kb 5' to the alpha 2-globin gene; this polymorphic site was observed for 10 of 38 non-alpha-thalassemia chromosomes from Black Americans. In four Black families with a heterozygous alpha-thalassemia-2 [-alpha 3.7 (I)], an Apa I restriction site has been identified in the IVS-2 of the alpha 2 gene of the normal chromosome (labeled the alpha *2 gene). The alpha *2 gene of one Black subject was cloned and a segment located 5' to the Cap site as well as the IVS-2, exon 3, and a 3' segment were sequenced. The data show that the alpha *2 gene is an alpha 2 gene except for a segment between nucleotides (nts) 580-81 and nt 509 (Cap site = nt 1), and perhaps as far upstream as nt -634, which has an alpha 1 sequence. This alpha *2 hybrid gene probably originated through a double crossover; the structural identity of its IVS-2 with that of the alpha 1 gene adequately explains the presence of the Apa I restriction site.
 ...
PMID:Detection of a new hybrid alpha 2 globin gene among American blacks. 289 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>