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)

The beta o-thalassaemia gene of an individual who was a mixed heterozygote for this allele (GAA to TAA in codon 121) and beta(+)-thalassaemia (IVS-1 position 110 G to A) was examined to determine if the beta o-thalassaemia allele directed the synthesis of any detectable protein product. This beta o-thalassaemia allele was of particular interest, because it is the only example of a premature chain termination codon in the third exon of the beta-globin gene that produces thalassaemia. A very small amount of an abnormal protein was found in the red blood cells of the proband and was purified by preparative column chromatography. This abnormal protein was digested with trypsin, the peptides were separated by reverse phase high performance liquid chromatography (HPLC), and the amino acid content of each peptide was determined. All of the soluble beta-globin peptides were found except for T-13, T-14 and T-15 (residues 121-146), indicating the presence of a truncated protein that corresponded to the translation product of the beta 121 Glu----Term mRNA. This truncated globin was estimated to comprise between 0.05% and 0.1% of the total non-alpha-globin protein. These results may explain the phenotype of inclusion body beta-thalassaemia in heterozygotes, which is atypical of heterozygous beta o-thalassaemia.
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PMID:Isolation and characterization of the translation product of a beta-globin gene nonsense mutation (beta 121 GAA----TAA). 220 8

We have studied a nuclear family containing a single child with severe beta-thalassemia intermedia, a Greek-Cypriot mother with hematological findings of beta-thalassemia trait, and a Polish father who is hematologically normal. Since both the child and her father were heterozygous for a DNA polymorphism within the beta-globin gene, it was possible to clone and sequence the beta-globin gene identical by descent from both the child and her father. A nonsense mutation in codon 121 (GAA----TAA) was found in the beta-globin gene of the child, while the same gene from her father lacked this mutation and was normal. This mutation has not been previously observed among over 200 beta-thalassemia genes characterized in Caucasians. Since the mutation eliminates an EcoRI site in the beta-globin gene, we could show that the mutation is not present in genomic DNA of the father. To rule out germinal mosaicism, sperm DNA of the father was also digested with EcoRI, and the mutant EcoRI fragment was not observed under conditions that would detect the mutation if it were present in at least 2% of sperm cells. Routine HLA and blood group testing supported stated paternity. In addition, studies with 17 DNA probes that detect multiple allele polymorphisms increased the probability of stated paternity to at least 10(8):1. These data provide evidence that the G----T change in codon 121 of the beta-globin gene in the child is the result of a spontaneous mutation that occurred during spermatogenesis in a paternal germ cell.
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PMID:Characterization of a spontaneous mutation to a beta-thalassemia allele. 301 70

Characterization of beta-thalassemia mutations was attempted for 13 unrelated Japanese patients heterozygous for beta-thalassemia. We have systematically analyzed beta-thalassemia genes using polymerase-chain-reaction-related techniques; dot blot hybridization with oligonucleotide probes complementary to known mutations, restriction endonuclease assay and direct sequencing of amplified genomic DNA. Seven different mutations were detected. Six of them are an amber mutation in codon 90 (GAG to TAG), a four-base-pair deletion in codons 41 and 42 causing premature termination due to frameshift, a C-T substitution at position 654 of IVS-2, a G-A substitution at position 1 of IVS-2 and a C-G substitution at position 848 of IVS-2, leading to splicing defects, and an ocher mutation (GAA-TAA) in codon 121 causing a thalassemia intermedia phenotype with inclusion body formation in erythrocytes. A silent mutation (CTG-TTG) was also detected in codon 91 of the allele with the IVS-2 position 1 mutation. These mutations have been reported previously in the Japanese population. The other mutation is a novel one in the Japanese, an amber mutation (TGG-TAG) in codon 15, causing a beta zero-thalassemia phenotype by premature termination of the beta-globin chain synthesis. We analyzed haplotypes of chromosomes bearing each beta-thalassemia mutation. Origins and a spectrum of mutations in comparison with those detected in malaria-endemic regions are discussed.
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PMID:Molecular basis of beta-thalassemia in Japan: heterogeneity and origins of mutations. 809 35

We detected Hb D-Los Angeles [beta 121(GH4)Glu-->Gln], the most common hemoglobin variant after Hb S and Hb Lepore-Boston, in six unrelated families in Southern Italy. Ten patients were studied; eight patients were heterozygotes and two were compound heterozygotes for the hemoglobin variant and the beta-thalassemia codon 39 (C-->T) nonsense mutation. The beta-globin gene sequence was characterized by polymerase chain reaction direct sequencing; restriction fragment length polymorphisms were defined by Southern blot analysis. The gene variant, due to the GAA-->CAA substitution at codon 121, was found in association with the 5' subhaplotype [+ - - - -] and the beta-globin gene framework 1; in addition, it was found to be associated with the absence of Ava II/phi beta and Xmn I/5'G gamma, and with the presence of Hpa I/3' beta. This restriction fragment length polymorphism haplotype is common in the Mediterranean area as well as in other populations. The findings are equally compatible with an independent origin in the Mediterranean area or with origin in Asia and subsequent spread to Italy.
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PMID:DNA polymorphisms associated with Hb D-Los Angeles [beta 121(GH4)Glu-->Gln] in southern Italy. 809 30

Hb Seal Rock was first reported in a young African-American women and her 2-year-old daughter (1). It is an extended alpha chain variant which, like Hb Constant Spring, is present in small quantity and is expressed as an alpha-thalassemia. The mutation, TAA-->GAA affects codon 142 of the alpha 2 gene. In this family, the index case was a compound heterozygote for Hb Seal Rock trait and for alpha-thalassemia trait (-3.7 kb). Her hematologic expression was similar to mild Hb H disease, presumably because the Seal Rock mutation affects the alpha 2 gene that is normally responsible for approximately 70% of alpha-globin synthesis. Her daughter had only Hb Seal Rock trait, but was phenotypically alpha-thalassemia-2 trait due to the expression of the Seal Rock mutation on one of her alpha 2-globin genes, the other three alpha-globin genes being unaffected.
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PMID:Hb Seal Rock [(alpha 2)142 term-->Glu, codon 142 TAA-->GAA]: an extended alpha chain variant associated with anemia, microcytosis, and alpha-thalassemia-2 (-3.7 Kb). 925 12

Among 13,525 haemoglobin analyses performed in our laboratory we detected 21 cases of haemoglobin D (Hb D) disease. Investigation of a family affected with this abnormal haemoglobin revealed two cases of Hb D/beta-(0) thalassaemia for the first time among Saudi Arabs. The two patients were diagnosed as having chronic haemolytic anaemia of moderate severity on the basis of the haemoglobin level, haematocrit, mean corpuscular haemoglobin, mean corpuscular volume, reticulocyte count, red blood cell count microscopy, elevated serum conjugated and non-conjugated bilirubin, increased serum lactic dehydrogenase, and the occasional need for blood transfusions. Genetic analysis enabled the detection of compound heterozygosity for the missense E121Q (codon 121 GAA-->CAA) and stop W15X (codon 15 TGG-->TGA) mutations as causative of the clinical phenotype of Hb D-LosAngeles (Punjab)/beta-(0) thalassaemia. The disease manifested as domination of Hb D and moderate haemolytic anaemia. The co-inheritance of beta-(0) thalassaemia seems to be responsible for conferring the deleterious effect on the presentation of Hb D disease in these patients. The present result emphasizes the significance of molecular testing in resolving certain diagnostic ambiguities in haematology as in cases of heterozygous Hb D in association with beta-(0) thalassaemia which, by haemoglobin electrophoresis, may be misdiagnosed as Hb D homozygosity.
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PMID:The beta-globin genotype E121Q/W15X (cd121GAA-->CAA/cd15TGG-->TGA) underlines Hb d/beta-(0) thalassaemia marked by domination of haemoglobin D. 1175 20

A 30-year-old female who is homozygous for a Hb E-like abnormal hemoglobin and her immediate relatives were studied. Clinical examination of the proband revealed no abnormality. Routine hematological analysis showed that her hemoglobin level was 12 g/dL, MCV 82 fL, MCH 28 pg, RDW 15%. DNA sequence analysis indicated the presence of a G-->A substitution at codon 22 corresponding to an abnormal hemoglobin, namely Hb E-Saskatoon [beta22(B4)Glu-->Lys (GAA-->AAA)]. Absence of any abnormalities in clinical and routine hematological investigations of the homozygous patient indicated that the phenotypical expression of the Hb E-Saskatoon is very mild. Using a reverse transcription-polymerase chain reaction technique, the alpha/beta and betaX/betaA-mRNA (X = Hb E-Saskatoon) ratios were determined. Normal alpha/beta and betaX/betaA-mRNA ratios were found in the homozygous patient and in all heterozygotes, indicating that the respective mutation did not alter the stability of the mRNA. FokI restriction enzyme analysis of the polymerase chain reaction products obtained from the genomic DNA and/or beta-globin mRNA made it possible for rapid diagnosis of Hb E-Saskatoon, and for its differentiation from Hb E [beta26(B8)Glu-->Lys (GAG-->AAG)]. Analysis of the restriction fragment length polymorphism (RFLP) in the beta-globin gene complex of the index patient and of another unrelated family with a compound heterozygosity for Hb E-Saskatoon and beta-thalassemia revealed that the Hb E-Saskatoon mutation shared a common allele.
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PMID:Homozygosity for Hb E-Saskatoon [beta22(B4)Glu-->Lys] in a Turkish patient. 1179 74

We describe the hematological and DNA characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand. Nine patients from five unrelated families were studied; four patients were simple carriers of Hb D-Punjab, two were compound heterozygotes for Hb D-Punjab/beta+-thalassemia; another two patients were double heterozygotes for Hb D-Punjab and alpha-thalassemia-2, and one patient was a compound heterozygote for Hb D-Punjab and Hb E [beta26(B8)Glu-->Lys]. Typical thalassemic indices with hypochromic microcytosis were observed in compound Hb D-Punjab/ beta+-thalassemia and Hb D-Punjab/Hb E but normal hematological profiles were observed in the remaining cases. DNA sequencing of the beta-globin gene identified the GAA-->CAA substitution at codon 121 causing Hb D-Punjab in all cases, and the -28 (A-->G) mutation for the beta+-thalassemia alleles. beta-Globin gene haplotype analysis demonstrated, for the first time, that all these Asian beta(D-Punjab) globin genes were associated with haplotype [-++-+++], previously undescribed in other populations. The finding of Hb D-Punjab in Thailand is compatible either with an independent origin of this abnormal hemoglobin or a spread of the Hb D-Punjab gene with a single origin among Asians.
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PMID:Molecular characterization of Hb D-Punjab [beta121(GH4)Glu-->Gln] in Thailand. 1240 91

The beta-globin gene mutations and the alpha-globin genes of 620 patients with the phenotype of severe to moderate thalassaemia from seven centres in Sri Lanka were analysed. Twenty-four beta-globin gene mutations were identified, three accounting for 84.5% of the 1240 alleles studied: IVSI-5 (G-->C) 56.2%; IVSI-1 (G-->A) 15.2%; and haemoglobin E (codon (CD)26 GAG-->GAA) 13.1%. Three new mutations were found; a 13-bp deletion removing the last nucleotide in CD6 to CD10 inclusively, IVSI-129 (A-->C) in the consensus splice site, and a frame shift, CD55 (-A). The allele frequency of alpha+ thalassaemia was 6.5% and 1.1% for -alpha3.7 and -alpha4.2 deletions respectively. Non-deletion alpha-thalassaemia was not observed. Triplicate or quadruplicate alpha-globin genes were unusually common. In 1.5% of cases it was impossible to identify beta-thalassaemia alleles, but in Kurunegala detailed family studies led to an explanation for the severe thalassaemia phenotype in every case, including a previously unreported instance of homozygosity for a quadruplicated alpha-globin gene together with beta-thalassaemia trait. These findings have implications for the control of thalassaemia in high-frequency populations with complex ethnic histories.
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PMID:The molecular basis for the thalassaemias in Sri Lanka. 1275 11

Thalassemias and hemoglobinopathies are very common among Southeast Asian populations, particularly in Thailand, where it is estimated that nearly 30% of the population carries at least one such disorder. Moreover, the heterogeneity of different mutant alpha- and beta-globin alleles contributes to the complexity in diagnosis and proper management, as more than 60 thalassemia syndromes and hemoglobinopathies have been described. Herein we report a further case of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] (also known as G-Saskatoon, G-Hsin Chu and G-Taegu) in a Thai family in which the mother was found to have an unusual hemoglobin (Hb) anomaly in combination with Hb E [beta26(B8)Glu-->Lys, GAG-->AAG]. We applied our recently described polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to scan the beta-globin genes and found an aberrant pattern in exon 1. The molecular analysis by direct genomic sequencing successfully identified the nucleotide mutation (codon 22, GAA-->GCA), and a novel amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for this variant is described.
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PMID:Further identification of Hb G-Coushatta [beta22(B4)Glu-->Ala (GAA-->GCA)] in Thailand by the polymerase chain reaction-single-strand conformation polymorphism technique and by amplification refractory mutation system-polymerase chain reaction. 1736 10


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