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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a novel alpha-thalassaemia-1 deletion that removes the entire zeta-alpha globin gene cluster. A Chinese couple were referred for counselling after two consecutive pregnancies ended with fetal hydrops. Gene mapping was used to demonstrate that the mother is heterozygous for the South-east Asia alpha-thalassaemia-1 deletion (zeta zeta zeta alpha alpha/zeta zeta--SEA), while the father carries an alpha-thalassaemia-1 deletion of more than 100 kilobases (zeta zeta alpha alpha/----). This newly discovered deletion extends for unknown distances 3' and 5' of the zeta-alpha globin gene cluster and has been designated (--HW).
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PMID:Identification of an extensive zeta-alpha globin gene deletion in a Chinese individual. 158 Dec 18

zeta-Globin chain expression in carriers of a number of deletional alpha-thalassemias is investigated by radioimmunoassay. In a few cases, zeta-globin mRNAs are also studied. zeta-Globin chains are detected in (--SEA/), (--MED/), and (--SPAN/) deletions, but not in six other deletional mutations. These results suggest that the DNA element capable of suppressing zeta-globin expression in adult erythroid cells is present within the (--SPAN/) deletion, while the DNA fragment between the 5' breakpoints of the (--SA/) and the (--SEA/) deletions may contain sequences necessary for augmenting zeta-globin expression in adult erythroid cells. Furthermore, zeta-globin chains are shown by an immunocytologic technique to be present in all circulating erythrocytes in carriers of the (--SEA/) and (--MED/) deletions. This simple immunocytologic test is highly sensitive and specific to detect adult carriers of either the (--SEA/) or (--MED/) deletions, and can be used for the detection of couples at risk of pregnancies involving fetuses with homozygous alpha-thalassemia.
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PMID:Human embryonic zeta-globin chain expression in deletional alpha-thalassemias. 162 4

alpha-Thalassemia hydrops fetalis is a common disorder in Taiwan. The condition causes perinatal death and many maternal obstetrical complications. In order to determine the molecular defects of this condition in Chinese, 87 unrelated families with this disorder were collected in the past 4 years. The molecular defects were studied by Southern blotting and DNA hybridization with phi zeta 1-globin gene and LO (a 0.4 kb BamHI/EcoRI fragment in the 5' flanking region of the zeta 2-globin gene) probes. Eighty-one (93.1%) fetuses had homozygous Southeast Asian deletion (- -SEA/- -SEA). Five (5.7%) fetuses were compound heterozygotes for the Southeast Asian deletion and Thailand deletion (- -SEA/- -THAI). The remaining fetus was a compound heterozygote for the Southeast Asian deletion and an uncharacterized nondeletional defect (- -SEA/(alpha alpha)Th). The molecular defects of alpha-thalassemia hydrops fetalis in Chinese are heterogeneous. This fact has important implications for genetic counseling and prenatal diagnosis.
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PMID:Molecular characterization of severe alpha-thalassemias causing hydrops fetalis in Taiwan. 186 84

The frequency of alpha-thalassemias in a general population sample from northeastern Thailand and in an Austroasiatic group with high frequencies of hemoglobin E and beta-thalassemia, the So, was estimated using DNA techniques. Among 64 healthy adult subjects from the Khonkaen and Ubol areas, the following haplotype frequencies were determined: alpha alpha, 0.742; -alpha 3.7 (subtype I), 0.148; -alpha 4.2, 0.016; -alpha del, 0.008; alpha Constant Spring alpha, 0.055; --SEA, 0.023, and alpha alpha alpha (triplicated alpha-globin gene), 0.008. In the So group, the combined frequency of alpha-thalassemia chromosomes was 0.525.
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PMID:Study of alpha-thalassemia in northeastern Thailand at the DNA level. 233 70

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual haematimetric values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha zero-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha(+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (- -MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (- -SEA) and (- -SPAN) and the "no-deletion" thalassaemias.
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PMID:[Analysis of a program for atypical familial microcytosis. Molecular basis for alpha-thalassemia. GEHBTA]. 236 92

The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine-labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population.
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PMID:Detection of the hemoglobin E mutation using the color complementation assay: application to complex genotyping. 237 88

A sensitive and specific radioimmunoassay (RIA) for human embryonic zeta-globin chains was used to study normal fetal blood and newborn cord blood as well as cord blood from newborns with alpha-thalassemias. From 17 weeks until 37 weeks of gestation, zeta-globin chains were present in almost all fetal and cord blood samples (0.27% +/- 0.15% in samples of weeks 17 through 30; 0.14% +/- 0.11% in samples of weeks 31 through 37). zeta-Globin chains were present in greater than 80% of cord blood hemolysates from normal, full-term newborns (0.15% +/- 0.11%) as well as from 16 near-term newborns of diabetic mothers (0.13% +/- 0.13%). zeta-Globin chains were not detected in normal infants aged 3 months to 2 years. In cord blood hemolysates from alpha-thalassemic newborns, the levels of zeta-globin chain content varied from very high to undetectable levels. Gene mapping of the zeta-alpha-globin gene cluster was performed in 12 newborns in whom cord blood zeta-globin chains had been determined. Newborns who were carriers of alpha-thalassemia-1 due to the (--SEA/) deletion had very high levels of zeta-globin chains (greater than 1.5%).
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PMID:Human embryonic zeta-globin chains in fetal and newborn blood. 247 89

In a gene mapping study on 217 newborn babies in Taiwan with alpha- and zeta-globin probes, we have observed 4 cases (1.84%) of alpha-thalassemia-2 heterozygotes (zeta zeta-alpha/zeta zeta alpha alpha) without increased levels of hemoglobin (Hb) Bart's in the cord blood. Eleven subjects (5.07%) were found to have the South East Asian alpha-thalassemia-1 haplotype (zeta zeta--SEA/zeta zeta alpha alpha) with increased Hb Bart's levels ranging from 2.2 to 9%. One case, with Hb Bart's level of 14% in the cord blood, was found to have the genotype of zeta zeta--SEA/zeta zeta alpha alpha T (0.46%). Four heterozygotes (1.84%) were found with the triple alpha gene anti-rightward arrangement (zeta zeta alpha alpha alpha 3.7/zeta zeta alpha alpha). Twenty-one heterozygotes (9.68%) were found to have the triple zeta-globin gene arrangement (zeta zeta zeta alpha alpha/zeta zeta alpha alpha). A new triple zeta-globin gene variant with a BamHI polymorphism was also observed in this study.
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PMID:Arrangements of alpha-globin gene cluster in Taiwan. 250 97

Hemoglobin H disease is often caused by deletion of three of the four alpha-globin genes (genotype: --/-alpha). We studied a Japanese girl who had microcytic hypochromic anemia, a decreased alpha/beta globin synthetic ratio and about 8% Hb H in her fresh hemolysate, by means of restriction endonuclease mapping of the alpha-like gene complex (5'-zeta-phi zeta-phi alpha 2-phi alpha 1-alpha 2-alpha 1-theta-3') with zeta- and alpha-specific probes. It was found that the defect of one chromosome was associated with the removal of about 18 kb of DNA, known as --SEA type alpha-thalassemia-1, including the deletion of the part of phi alpha 2, phi alpha 1, alpha 2, alpha 1, and theta globin genes, while the other one was associated with the removal of 3.7 kb of DNA, known as rightward deletion type alpha-thalassemia-2. The results of a family study demonstrated that the deletion haplotype --SEA was inherited from her father's side and the other -alpha 3.7 from her mother's side.
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PMID:[The molecular basis of HbH disease in a Japanese girl]. 261 58

Details are presented of analyses of hemoglobins in blood samples from four newborn babies with hydrops fetalis using reversed phase and anion exchange high performance liquid chromatographic methodology. Three were homozygous for the alpha-thalassemia-1 (SEA) deletion, and one was a compound heterozygote for the same deletion and the larger alpha-thalassemia-1 (Fil) deletion. All four babies had beta, G gamma, A gamma, and zeta chains; these chains were present in Hb Bart's or gamma 4, Hb Portland-I (zeta 2 gamma 2), and Hb Portland-II (zeta 2 beta 2). Hb H (beta 4) could not be detected. The level of zeta was directly related to the level of beta and, thus, the fetal age. A lower level of zeta chain was present in the baby with the compound heterozygosity because the large deletion (Fil) on one chromosome included the zeta and psi zeta genes. Circulating red cells, i.e. reticulocytes and nucleated red cells, were unable to synthesize zeta chains, indicating that this capability must have ceased a few months prior to birth. Quantitative data obtained by chromatographic procedures were greatly influenced by the condition of the blood sample and the way it was stored. Hb Portland-II (zeta 2 beta 2) and Hb Bart's (gamma 4) are rather unstable when a red cell lysate is stored at 4 degrees C; this is in contrast to Hb Portland-I (zeta 2 gamma 2) which appears to be stable. Samples can be stored as washed red cells or red cell lysates at -70 degrees C.
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PMID:The types of hemoglobins and globin chains in hydrops fetalis. 263 68


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