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)

Sequence analyses of amplified DNA from a Yugoslavian patient with Hb Lepore-beta-thalassemia and from his father with a simple beta-thalassemia trait have revealed a T----A mutation within the ATA box at a position 30 base pairs upstream from the Cap site. The nucleotide substitution was confirmed through dot-blot analysis of amplified DNA with specific 32P-labeled synthetic oligonucleotide probes. The patient had a clinically severe condition; his Hb Lepore-beta-thalassemia was of the beta + type, as about 8-10% of the non-alpha chain was normal beta A. The same T----A mutation at nucleotide -30 was present on both chromosomes of a young Turkish patient who suffered from a thalassemia intermedia with a low level of Hb F (13.1%) and a relatively high beta A chain synthesis. These data are similar to those obtained for other types of beta +-thalassemia caused by comparable substitutions at positions 31, 29, and 28 base pairs upstream from the Cap site of the beta-globin gene.
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PMID:Beta-thalassemia due to a T----A mutation within the ATA box. 338 1

The beta-globin gene clusters of three unrelated Thai families with a nondeletional type of hereditary persistence of fetal haemoglobin (HPFH) were studied using polymerase chain reaction-related techniques. All appeared to have normal nucleotide sequences from the Cap site to position -400 of both the G gamma- and A gamma-globin genes. Two individuals suspected of having a beta-thalassaemia gene linked to the high HbF condition also had a normal beta-globin gene sequence, spanning from position -108 from the Cap site to the polyadenylation site. Deletion of four nucleotides, AGCA, at positions -225 to -222 of one A gamma-globin allele was detected in one subject and was confirmed by dot-blot hybridization. Restriction fragment length polymorphisms in the beta-globin gene cluster showed that the 5' haplotype (-+-++) and the presence (+) of an Xmm 1 polymorphic site at -158 of the G gamma-globin gene are associated with the high F phenotype in these families. Direct sequencing of the 5' hypersensitive-2 (5' HS-2) site of the locus control region (LCR) showed that this Xmn 1 (+) site is also linked to a specific rearrangement of TA repeats (TA)9CACATATACG(TA)10, in HS-2 segment.
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PMID:Nondeletional type of hereditary persistence of fetal haemoglobin: molecular characterization of three unrelated Thai HPFH. 752 42

We describe an African-American child with beta-thalassemia intermedia. Molecular studies revealed that the proband is a compound heterozygote for the -29 (A-->G) beta (+)-thalassemia mutation and an extensive deletion involving the delta- and beta-globin genes. The proband's mother is a simple carrier of the deletion and exhibits the phenotype of delta beta-thalassemia rather than hereditary persistence of fetal hemoglobin. The deletion spans 11,767 bp, with the 5' deletion endpoint located 2,455 bp upstream of the delta-globin gene mRNA Cap site and the 3' endpoint located 441 bp downstream of the termination codon of the beta-globin gene. Based on this information, we have developed a polymerase chain reaction strategy for the rapid detection of this delta beta-thalassemia deletion.
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PMID:Delta beta-thalassemia in an African-American: identification of the deletion endpoints and PCR-based diagnosis. 771 43

A large novel alpha-thalassemia-1 deletion which includes the zeta-, alpha 2-, alpha 1-, and theta 1-globin genes is described in a Black family living in Georgia and Florida. The deletion which was characterized by restriction enzyme analysis, extends 15 to 35 kb 5' and at least 35 kb 3' to the Cap site of the zeta-globin gene. Mental retardation was not observed. The deletion was present in a 35-year-old male with Hb H disease and his mother; the major hemoglobin type in the propositus was Hb G-Philadelphia or alpha (2)68(E12)Asn-->Lys beta 2 because his second chromosome carried the -alpha G(-3.7 kb) alpha-thalassemia-2 deletion.
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PMID:Black alpha-thalassemia-1: partial characterization of an approximately 80 kb deletion which includes the zeta- and alpha-globin genes. 790 Nov 83

Using the technique of allele-specific priming of the polymerase chain reaction (PCR), the C-T substitution in codon 39 was identified as the cause of beta-thalassaemia in an Irish family. Analysis of the restriction fragment length polymorphisms (RFLPs) in the beta-globin gene cluster established linkage of the beta-thalassaemia mutation to a particular beta-haplotype but indicated that a recombinational event had occurred in the paternal chromosome in the younger of two affected children. Non-paternity was excluded by DNA fingerprinting analysis with hypervariable minisatellite probes. This is the fourth case of recombination in the beta-globin gene cluster to be reported. The event has occurred 5' of the polymorphic RsaI site at position -550 bp upstream of the beta-globin gene mRNA Cap site, within the 9.1-kb region that has been shown to be a hot spot for recombination in the beta-globin gene cluster.
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PMID:Meiotic recombination in an Irish family with beta-thalassaemia. 810 2

In 1991 we reported the identification of two deletional alpha-thalassaemia-2 determinants (-3.7 kb and -4.2 kb) and one nondeletional alpha-thalassaemia-2 determinant (Hb Koya Dora alpha 2 codon 142, TAA-->TCA) in a tribal population in Central India (Gupta et al, 1991). Evidence was obtained at that time for the possible presence of an additional nondeletional alpha-thalassaemia-2 because of low levels of Hb S (< 28%) in some Hb S heterozygotes with a simple alpha-thalassaemia-2 heterozygosity (-alpha/alpha alpha). This abnormality has now been identified as a G-->A mutation at IVS-I-117 of the alpha 1-globin gene (acceptor splice site) which makes this gene nonfunctional. Its frequency was established at approximately 6% which raises the total frequency of alpha-thalassaemia determinants in this population to approximately 60%. Subjects with a deletional alpha-thalassaemia-2 and the newly discovered alpha 1 acceptor splice junction mutation in trans appear to have an alpha chain deficiency similar to that of an alpha-thalassaemia-2 homozygote (-alpha/-alpha). An additional change (C-->G) at the Cap -4 site was observed in six alpha 1- and one alpha 2-globin genes; this polymorphism is not associated with a decrease in alpha chain synthesis and is not linked to the IVS-I-117 (G-->A) mutation.
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PMID:An IVS-I-117 (G-->A) acceptor splice site mutation in the alpha 1-globin gene is a nondeletional alpha-thalassaemia-2 determinant in an Indian population. 825 82

The beta-thalassemias are a heterogeneous group with respect to molecular pathogenesis, and different populations and ethnic groups differ with respect to the predominating mutations. This variable spectrum of beta-thalassemia mutations has resulted in extensive studies in each population and ethnic group to identify the major mutations. In this study we investigated the prevalence of 14 mutations in 253 beta-thalassemia patients drawn from eight Arab countries (i.e. Jordan, Egypt, Syria, Lebanon, Yemen, and Saudi Arabia), living in Saudi Arabia and attending Ministry of Health hospitals. The mutations investigated included IVS-I-110 (G-->A), IVS-II-1 (G-->A), IVS-I-5 (G-->C), codon 39 (C-->T), IVS-I-1 (G-->A), frameshift at codons 8/9 (+G), frameshift at codons 41/42 (-TTCT), codon 15 (TGG-->TAG), IVS-I-6 (T-->C), frameshift at codon 16 (-C), IVS-II-745 (C-->G), codon 6(-A), IVS-I, 3' end (-25 bp), and Cap +1 (A-->C). The most frequently encountered mutations were IVS-I-110 and IVS-II-1 which were identified in the population of each Arab country. The IVS-I-1 and IVS-II-745 mutations were encountered in Jordanians, Egyptians, and Syrians. The IVS-I-5, codon 39, codon 6, IVS-I, 3' end (-25 bp), and Cap +1 mutations were encountered only in Saudis and not in other Arabs, except codon 39 which was present in the Syrians and Lebanese. Other mutations were generally rare and not specific to any Arab ethnic group. This paper presents preliminary data on the prevalence of 14 mutations in the Arab populations and shows wide variation in the molecular basis of beta-thalassemia in different Arab ethnic groups. Further detailed studies to identify the entire spectrum of beta-thalassemia mutations are stressed.
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PMID:The frequency of 14 beta-thalassemia mutations in the Arab populations. 871 94

The partial molecular characterization of a large deletion present in two members of an Indonesian-Malay family with beta-thalassemia trait is described. Polymerase chain reaction and sequencing analyses of the breakpoint identified a sequence which has previously been described in patients with the 45 kb Filipino beta 0-thalassemia deletion, i.e. a 5' breakpoint at position -4279 nucleotides 5' from the Cap site of the beta-globin gene. The 3' breakpoint is located in an L1 family of repetitive sequences at an unknown distance from the beta-globin gene. The hematological and hemoglobin data of the patients with this beta 0-thalassemia deletion further supports the concept that the unusually high Hb A2 levels are unique to deletions removing the 5' beta-globin gene region, and points to the importance of the 3' junction sequences for the regulation of Hb F levels in patients with deletional defects of the beta-globin gene cluster.
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PMID:A large beta-thalassemia deletion in a family of Indonesian-Malay descent. 893 64

We have offered first trimester prenatal diagnosis to 55 couples at risk for beta-thalassemia, originating from various parts of India, using polymerase chain reaction and denaturing gradient gel electrophoresis. Apart from the six common mutations, codon 30 (CAG-->CAA), Cap site +1 (A-->C), as well as three uncharacterized mutations were seen among the parents. In the majority of cases, the diagnosis was possible by scanning only one fragment (B) where most of the Indian mutations are situated. In 18 out of 55 cases, framework analysis could also have been used to offer prenatal diagnosis without characterizing the beta-thalassemia mutations. In the two cases where the mutations were uncharacterized, prenatal diagnosis was done only on the basis of the anomalous denaturing gradient gel electrophoresis patterns seen in the parents and in previously affected children. This is the first attempt of prenatal analysis using denaturing gradient gel electrophoresis in the extremely diverse Indian population where the profile of mutations has not yet been fully elucidated.
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PMID:Prenatal diagnosis of beta-thalassemia among Indians using denaturing gradient gel electrophoresis. 932 77

We report the clinical, haematological, biosynthetic and molecular data of 25 double heterozygote beta-thalassaemia intermedia patients and 45 beta-thalassaemia heterozygotes with the C --> T substitution at nucleotide position -101 from the Cap site, in the distal CACCC box of the beta-globin gene promoter. This mutation is considered the most common amongst the silent beta-thalassaemia mutations in Mediterranean populations. Of the 25 compound heterozygotes for the beta -101 C --> T and common severe beta-thalassaemia mutations, all but one had mild thalassaemia intermedia preserving haemoglobin levels around 9.5 g/dl and haemoglobin F levels < 25%. The only transfused patient was characterized to have an additional alpha-globin gene. Strict assessment of haematological and biosynthetic findings in the heterozygotes for the beta -101 C --> T mutation (excluding six cases with an alpha-globin gene defect) demonstrated that less than half of them had completely normal (silent) haematology; the remainder had either high haemoglobin A2 values (in the range of 3.7-5.1%) and/or low red cells indices and/or raised haemoglobin F values. The alpha/non-alpha-globin chain synthesis ratios were generally raised, with mean 1.44 (1.07-2.10). Amongst the parents of the compound heterozygotes, who were not selected for molecular analysis following haematological screening, half of the cases were completely silent. Interaction with severe beta-thalassaemia mutations always resulted in the clinical phenotype of mild non-transfusion-dependent thalassaemia intermedia.
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PMID:Molecular, haematological and clinical studies of the -101 C --> T substitution of the beta-globin gene promoter in 25 beta-thalassaemia intermedia patients and 45 heterozygotes. 1060 72


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