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

A study for screening of beta-thalassaemia mutations by the Amplification Refractory Mutation System (ARMS) and haplotyping by Polymerase Chain Reaction (PCR) was undertaken because there was a paucity of data in Tamil Nadu in Southern India and to initiate a comprehensive prenatal diagnosis programme. A total of 294 alleles were analysed to study the nature of the mutations, of which 146 were beta-thalassaemia alleles. Only four types of beta-thalassaemia mutations were recorded. Of these, 128 alleles were of the variant IVS-1 nt 5 (G-->C). Thirteen had the mutation codon 41/42 (del TCTT), four had the mutation codon 8/9 (insert G) and one had the 619 bp deletion at the 3' end of the gene. The most common mutation, IVS-1 nt 5 (G-->C), was strongly associated with a single haplotype although the association was not absolute. The population of Tamil Nadu in Southern India seems to be ideal for initiating a prenatal diagnosis programme based on direct detection of mutation by ARMS coupled with RFLP linkage analysis.
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PMID:beta-Thalassaemia mutations and their linkage to beta-haplotypes in Tamil Nadu in southern India. 136 29

Prenatal diagnosis is available for pregnancies at risk for virtually all inherited disorders of hemoglobin production. The field of reproductive genetics must confront many ethical, legal, and social concerns regarding its use, many of which derive from a woman's desire to bear children but legal right to abortion. The goal of more widespread utilization of prenatal diagnosis is sought in the context of questioning the ethical control to be exerted over the biological makeup of future generations. Its appropriate application would be facilitated greatly by the availability of reliable DNA markers of disease severity. Advances in fetal sampling and in detecting mutant globin genes have provided the safe, accurate methodology required for prenatal diagnosis. Chorionic villus sampling in the first trimester has become standard practice, but second trimester amniocentesis also is used for sampling fetal DNA. The use of preimplantation diagnosis and testing fetal cells from the maternal circulation will soon be practical. DNA-based detection of globin gene mutations has been facilitated greatly by the polymerase chain reaction revolution, and several reliable diagnostic methods are available. Polymerase chain reaction-based methods rely on restriction analysis, allele-specific hybridization or amplification, DNA sequence analysis, and new non-polymerase chain reaction methods for DNA amplification in vitro. These methods are available for detecting hemoglobinopathy, thalassemia, and thalassemic-hemoglobinopathy genes that affect alpha- or beta-globin loci.
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PMID:Advances in the prenatal and molecular diagnosis of the hemoglobinopathies and thalassemias. 853 29

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

Polymerase chain reaction-based techniques were used to study the molecular defects of 480 unrelated beta-thalassemia heterozygotes in Taiwan. Analysis of artificially created restriction sites and gap-polymerase chain reaction were performed to detect four common mutations, i.e. IVS-II-654 (C-->T), codons 41/42 (-TCTT), codon 17 (A-->T), -28 (A-->G), and a deletional form of delta beta-thalassemia in the Chinese population. In cases with negative or ambiguous results with the aforementioned methods, direct DNA cycle sequencing using either S35-dATP or a fluorescent dye terminator, was carried out to determine the defects. A total of 14 different mutations have been found in this series. The IVS-II-654 mutation was the most common (39.6%), followed by the codons 41/42 mutation (37.9%). The four common genotypes accounted for 92.3% of defects. Two new mutations were detected: codon 31 (-C) and codons 40/41 (+T). Both defects resulted in a frameshift and a premature terminator, the former at codon 60, the latter at codon 43. Although we have studied our cases extensively, the molecular defects in seven alleles are still unknown.
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PMID:Molecular characterization of beta-thalassemia in Taiwan and the identification of two new mutations. 910 Dec 82

This article is the first report of hemoglobin (Hb) Pyrgos along with other Hbs forming triple-heterozvgous patterns. Of 2 cases, the first occurred in a Thai girl with thalassemic facies, marked anemia, and hepatosplenomegaly, who had Hb Pyrgos in association with Hb H disease with Hb Constant Spring (CS). This case represents a triple heterozygosity comprising Hb Pyrgos, alpha-thalassemia 1, and Hb CS. Hb electrophoresis revealed an abnormal Hb in addition to Hbs CS, A2, A, Bart's, and H. This abnormal Hb moved slightly faster than Hb A but more slowly than Hb Bart's. Polymerase chain reaction revealed that the abnormal Hb was caused by a missense mutation within codon 83 of the beta-globin gene (GGC to GAC) resulting in a glycine-to-aspartic acid substitution, which corresponds to Hb Pyrgos. The patient required blood transfusions by the age of 3 years. A splenectomy was performed when she was 5 years old, after which her hematocrit level remained above 32%. The second case was the patient's older sister who was also triple heterozygous (Hb Pyrgos, E, and CS) but was healthy.
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PMID:Triple heterozygosity of a hemoglobin variant: hemoglobin Pyrgos with other hemoglobinopathies. 1184 88

Two cases of the Thai thalassemia patients with compound heterozygosities for (deltabeta)(0)/beta(0)-thalassemia and (deltabeta)(0)-thalassemia/hemoglobin E have been reported. The first case was a 8-yr-old boy who had the following hematologic data: Hb 6.5 g/dL, Hct 20.5%, MCV 70.4 fL, MCH 22.3 pg and MCHC 31.7 g/dL. Hemoglobin analysis revealed 1.9% hemoglobin A2 and 91.7% hemoglobin F. The second case, with Hb 13.9 g/dL, Hct 41.5%, MCV 69.5 fL, MCH 22.5 pg and MCHC 32.2 g/dL, was a 16-yr-old male who had 46.1% hemoglobin E and 49.8% hemoglobin F. Globin gene analyses showed that both probands carried the same deletional type (deltabeta)(0)-thalassemia trans to the 4 bp deletions in codons 41/42 beta(0)-thalassemia and to the betaE-globin gene, respectively. Polymerase chain reaction and DNA sequence analyses demonstrated that the 5' breakpoint of the (deltabeta)(0)-thalassemia deletion was located in the second intron of the delta-globin gene and that the 3' breakpoint lay within a cluster of LI repetitive sequences at 4.7 kb 3' to the beta-globin gene.
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PMID:Molecular characterization of (deltabeta)(0)/beta(0)-thalassemia and (deltabeta)(0)-thalassemia/hemoglobin E in Thai patients. 1186 Apr 49

Hemoglobin (Hb) Korle-Bu (beta73; Asp-Asn) is the most frequent of the rare beta-chain variants in the population of West Africa whereas Hb E (beta26; Glu-Lys) is common among the Southeast Asian population. We report a hitherto undescribed condition in which these two beta-chain variants co-segregate. The proband was a 19-year-old Thai pregnant woman in her second trimester of pregnancy who visited our thalassemia screening unit. Cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC) analysis of Hb detected one abnormal Hb in addition to the Hb E. Analysis of DNA sequences revealed a GAT-AAT mutation at codon 73 in trans to a GAG-AAG mutation at codon 26 of the beta-globin gene. Polymerase chain reaction (PCR) analysis of the alpha-globin gene cluster of the patient detected a 3.7-kb deletional alpha-thalassemia 2. Family study identified that her mother had the same genotype and her father was a simple Hb E carrier. The hematological data of these unusual cases of hemoglobinopathy are presented and compared with a simple heterozygote for Hb Korle-Bu found in another unrelated Thai family. beta-Globin gene haplotype linked to the Thai beta(Korle-Bu) and a simple DNA assay based on allele-specific PCR for rapid diagnosis of Hb Korle-Bu are also described.
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PMID:Compound heterozygosity for Hb Korle-Bu (beta(73); Asp-Asn) and Hb E (beta(26); Glu-Lys) with a 3.7-kb deletional alpha-thalassemia in Thai patients. 1218 10

Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
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PMID:Molecular defects in the beta-globin gene identified in different ethnic groups/populations during prenatal diagnosis for beta-thalassemia: a Malaysian experience. 1559 63

JAK2 is a cytoplasmic tyrosine kinase that has a vital role in signal transduction from several hemopoietic growth factor receptors. The JAK2 V617F mutation has been implicated in a variety of diseases mainly related to myeloproliferative disorders including polycythemia Vera, essential thrombocythemia, and idiopathic Myelofibrosis but has not been previously described in Thalassemia patients. We studied 36 Lebanese patients diagnosed with thalassemia intermedia and assessed the presence or absence of the JAK2 V617F mutation using JAK2 activating mutation assay (In VivoScribe Technologies) and Polymerase Chain Reaction (PCR). None of the thalassemia intermedia patients were positive for this mutation. To our knowledge, this study is the first to determine the status of JAK2 V617F mutation in thalassemia intermedia patients and expands the international published literature on JAK2. The latter's V617F mutation does not seem to play a role in this hematologically important clinical entity.
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PMID:Absence of JAK2 V617F mutation in thalassemia intermedia patients. 1878 1

A method for detection of hemoglobin (Hb) E mutation was developed based on allelic discrimination analysis. Two probes labeled with different fluorescent reporter dyes were designed to specifically detect variation of a single nucleic acid polymorphism (SNP) site in the target template sequence. Polymerase chain reaction (PCR) products of normal allele and mutant allele were detected directly by analyzing fluorescent signal of each probe. This method was validated in term of accuracy (by comparing with sequence analysis) and reproducibility. The % CV between run precision was 5.16-8.86%. The narrow scatter of the results confirmed the reproducibility of the assay. This technique is a rapid, reliable and cost-effective method to differentiate Hb E homozygosity from beta(0)-thalassemia/Hb E in populations with a high frequency of beta-thalassemia and Hb E.
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PMID:Detection of Hb E mutation (beta(26), GAG-AAG, Glu-Lys) using allelic discrimination analysis. 1849 85


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