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)

We have studied a Portuguese family with a dominant beta-thalassaemia trait that was present in one member of each of three generations. It was characterized by a moderate anaemia, microcytosis and hypochromia, anisopoikilocytosis, Heinz body formation in peripheral red cells, splenomegaly, and a blood transfusion requirement during pregnancy. Sequence analyses of amplified DNA detected a deletion of (G) TG.GCT.GGT.GT(G) at codons 134-137 (Val.Ala.Gly.Val) and the insertion of (G)GC.AG(G) (Gly.Arg) at the same location. Thus, the resulting beta chain has an abnormal structure only at codons 134-137 and is two residues shorter than the normal 146 residues. This chain could not be detected in circulating red cells and must be degraded rapidly by proteolysis because the Heinz bodies consisted mainly of alpha chains.
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PMID:Dominant beta-thalassaemia trait in a Portuguese family is caused by a deletion of (G)TGGCTGGTGT(G) and an insertion of (G)GCAG(G) in codons 134, 135, 136 and 137 of the beta-globin gene. 165 62

Characterization of beta-thalassemia mutations were attempted for 29 Japanese families clinically diagnosed as having beta-thalassemia. Following the identification of a mutation by cloning and sequencing, all families were screened for this particular mutation, using biotinylated allele-specific oligonucleotide probes. Seven different mutations were detected in 17 families: Six families had the frameshift mutation at codons 41/42, resulting from a 4 nucleotide deletion (TTCTTT----TT); four had the deletion at codons 127/128 (CAGGCT----CCT); and three had the TATA box mutation at nucleotide -31 (A----G). Four additional families had mutations at codon 24 (GGT----GGA), codon 26 (GAG----AAG), IVS-II-654 (C----T) and codon 110 (GTG----CCG), respectively. The newly discovered deletion mutation at codons 127/128, and mutations at nucleotide -31, and at codon 110 are peculiar to Japanese, and have not been found in any other ethnic group. The haplotypes of the beta-globin gene cluster were also determined. Some of the haplotypes and beta-thalassemia mutations are identical to those reported in the Chinese population. However, it is noteworthy that nearly half of the beta-thalassemia mutations were unique to Japanese.
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PMID:Characterization of beta-thalassemia mutations among the Japanese. 263 67

A beta+-thalassemia mutation at codon 24 (GGT----GGA) was discovered in a Japanese; this is the third type of beta-thalassemia found in this population. The case, as well as the data from DNA sequencing analysis, are presented.
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PMID:A beta+-thalassemia (codon 24, GGT----GGA) found in a Japanese. 320 9

A beta+-thalassemia globin gene was isolated from the genome of a Black individual by molecular cloning. DNA sequence analysis revealed only a single difference between this gene and the normal human beta-globin gene--adenine is substituted for thymine in the third position of codon 24. Codon 24 in both the normal gene (GGT) and the beta+-thalassemia gene (GGA) encodes glycine. The function of this beta+-thalassemia gene was compared to the function of the normal human beta-globin gene in monkey kidney cells by using plasmid expression vectors. The codon 24 substitution activates a 5' splice site that involves the guanine-thymine dinucleotide present in codon 25, 16 nucleotides upstream from the normal exon 1-intron I boundary. The splice, involving the abnormal 5' site in codon 25, is completed with the normal 3' splice site at the end of intron I. This splicing abnormality leads to a 75% decrease in the accumulation of normally processed beta-globin mRNA, thereby causing the beta+-thalassemia phenotype.
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PMID:"Silent" nucleotide substitution in a beta+-thalassemia globin gene activates splice site in coding sequence RNA. 657 78

The proband is an elderly woman (79 years of age) of Surinamese-Hindustani origin, suspected of being a carrier of a nondeletional alpha-thalassemia (thal) because of a moderate microcytic hypochromic anemia at normal ferritin levels and in the absence of any other alpha-thal deletions. Sequence analysis revealed a silent mutation (GGC-->GGT) at codon 22 of the alpha2-globin gene. This mutation generates a splice donor site consensus sequence (GGTGAG) between codons 22 and 23. The abnormally spliced mRNA leads to a premature termination between codons 48 and 49. The presence of a downstream intron may induce the intracellular degradation of the affected mRNA, a pathway known as nonsense mediated decay (NMD), and this explains the alpha(+)-thal phenotype observed in the patient. The codon 22 (GGC-->GGT) transition described in this report is the first mutation creating a splice donor site in one of the alpha-globin genes.
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PMID:An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point mutation that creates an alternative splice donor site in the first exon of the alpha2-globin gene. 1548 95

We report the hematological and molecular characterization of compound heterozygosity for hemoglobin (Hb) Hope/Hb E and double heterozygosity for Hb Hope/ alpha-thalassemia 2 found in 2 unrelated Thai individuals. The first proband presented with slight anemia and mild hypochromic microcytosis. Routine cellulose acetate Hb electrophoresis at pH 8.6 revealed in addition to Hb E another variant migrating slightly more anodic to Hb A. On cation exchange high-pressure liquid chromatography, the variant was eluted in the amount of 60.9% after Hb E The same abnormal Hb was found in a second family in which the proband and her younger sister were both double heterozygotes for this Hb variant and deletional alpha-thalassemia 2, whereas an older sister was a pure carrier of the variant. The amounts of this variant were found to be 34.9%, 35.4%, and 38.3% in the proband, her younger sister, and her older sister, respectively. Direct DNA sequencing of the amplified beta-globin genes of both probands identified the GGT (Gly)-GAT (Asp) mutation at codon 136 corresponding to Hb Hope. beta-Globin gene haplotype analysis demonstrated that all the Thai betaHope genes were associated with the same haplotype, (+ - - - - + +), indicating a single origin of this variant in Thailand. A simple method based on allele-specific polymerase chain reaction for accurate diagnosis of the Hb Hope is described.
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PMID:Molecular and hematological characterization of hemoglobin Hope/hemoglobin E and hemoglobin Hope/alpha-thalassemia 2 in Thai patients. 1569 92

Hb Hope [beta136(H14)Gly --> Asp (GGT --> GAT)] has been found alone or in combination with other globin gene mutations in several African-American families, as well as in Japanese, Thai, Laotian, Cuban and Mauritanian families. We report the hematological and molecular characteristics of a heterozygous association of Hb Hope with beta0-thalassemia (thal) in a Spanish patient, in whom the level of expression of abnormal hemoglobin (Hb) by cation exchange high performance liquid chromatography (HPLC) and electrophoresis suggested initially a homozygous expression of the abnormal Hb, although sequencing of the polymerase chain reaction (PCR)-amplified beta-globin gene demonstrated a heterozygous genotype for Hb Hope. To the best of our knowledge, this is the first description of a case of Hb Hope in a Spanish family.
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PMID:Heterozygous Hb Hope [beta136(H14)Gly --> Asp] in association with heterozygous beta0-thalassemia with apparent homozygous expression, in a Spanish patient. 1654 Apr 15

To help clarify the hematological picture of patients who may be positive for beta- and delta-globin gene mutations, the following study was carried out. Our aim was to identify the delta-globin gene mutations found in the Greek Cypriot population, their frequencies and the Hb A2 values associated with them. Seventy-four samples were selected from a random sample of 5,030 individuals, and the database of the Molecular Genetics Thalassaemia Department containing diagnostic analyses data was also mined for relevant information. Four novel for Cyprus delta-globin gene mutations: -30 (T-->C), Hb A2-Wrens [delta98(FG5)Val-->Met, GTG-->ATG], IVS-I-2 (T-->C) and Hb A2-Yokoshima [delta25(B7)Gly-->Asp (GGT-->GAT)] were identified. Hb A2-Yialousa [delta27(B9)Ala-->Ser, GCC-->TCC], Hb A2-Yokoshima, Hb A2-Troodos [delta116(G18)Arg-->Cys, CGC-->TGC], Hb A2-Pelendri [delta141(H19)Leu-->Pro, CTG-->CCG], codon 4 [delta4(A1)Thr-->Ile], codon 59 (-A), Hb A2-Wrens, IVS-II-897 (A-->G), IVS-I-2, -55 (T-->C) and -30 bring the total to 11 delta-globin alleles found in the Greek Cypriot population. Hb A2-Yialousa is the most common mutation followed by codon 4, with frequencies of 60.7 and 17.8%, respectively.Hb A2 levels above 1.9% have been found to indicate a significantly reduced possibility for the presence of a delta-globin gene mutation in this population. For Hb A2 levels of 1.7 and 1.8% the possibility of a delta-globin gene mutation rises to 90.9% and reaches 100% for lower Hb A2 levels. The frequency of all the mutant delta-globin chromosomes in the sample is 0.0067 and the carrier frequency is 1.26%.
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PMID:Delta-thalassemia in Cyprus. 1698

Haemoglobin (Hb) Hope [beta136(H14)Gly-->Asp(GGT-->GAT)] is one of the unstable haemoglobin variants of the beta-globin chain, which is demonstrated in people of various ethnic backgrounds. Here we report a Thai female patient with clinical thalassaemia intermedia since childhood. This patient had experienced neither blood transfusion nor hospitalisation. Hb Bart's-H and a large amount of Hb Hope were identified by high-performance liquid chromatography (HPLC) assay and the diagnosis of homozygous Hb Hope was definitely achieved by direct sequencing of exon 3 of beta-globin gene. Furthermore, we could identify that her brother carried the mutation of homozygous Hb Hope without abnormal alpha globin chain involvement, and another family member had heterozygous Hb Hope in association with -alpha(3.7) mutation, and both of them were clinically silent.
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PMID:Haemoglobin Hope in a northern Thai family: first identification of homozygous haemoglobin Hope associated with haemoglobin H disease. 1765

Hb Dhofar is a variant haemoglobin (beta(29 (GGC-GGT) gly-gly), beta(58 (CCT-CGT) pro-arg)) associated with a thalassaemic phenotype and unique to the Sultanate of Oman. We report clinical and haematological data on 54 subjects with Hb Dhofar (37 heterozygotes, 14 homozygotes and three compound heterozygotes with a different beta-thalassaemia mutation). In heterozygotes, the level of Hb Dhofar ranged from 8.8% to 21.5%. All heterozygotes had Hb A2 > 3.5%, consistent with beta-thalassaemia trait. Hb Dhofar in homozygotes and compound heterozygotes ranged from 26% to 59.7%, with a peripheral film consistent with homozygous beta-thalassaemia. Age at presentation in homozygotes ranged between 6 months and 8 yr, with a majority presenting before 5 yr of age. All had splenomegaly and six (43%) had undergone splenectomy. All had some degree of frontal bossing and in particular, two patients with infrequent transfusions had marked thalassaemic facies and stunting of growth. Hb Dhofar can be mistaken for Hb D as the electrophoretic mobility is similar, but differs from it by a variable and reduced quantity of variant Hb in both heterozygotes and homozygotes. Clinical and haematological data suggest that this mutation behaves like a moderately severe beta(+) thalassaemia allele resulting in a thalassaemia intermedia phenotype.
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PMID:Haematological and clinical features of beta-thalassaemia associated with Hb Dhofar. 1817 41


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