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)

A new single nucleotide change at nt 2 of exon 1 of the beta-globin gene was identified in a Chinese female patient with beta-thalassaemia. Dot blot hybridization of the amplified genomic DNA with oligonucleotide probes showed that she carried the four base deletions at the codons 41/42. Direct DNA sequencing on the amplified DNA revealed that she also carried a new mutation (ATG-AGG) at the initiation codon on the other beta-globin gene. This single nucleotide change abolishes a NcoI recognition site and hence it can be directly visualized after gel electrophoresis. Analyses of restriction fragment length polymorphisms showed that she also carried a rightward -3.7 kb (type I) deletion in her alpha-globin genes, and is in fact a alpha beta-thalassaemia genotype.
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PMID:[New single point mutation at the initiation codon (ATG-AGG) identified in amplified genomic DNA of a Chinese with beta-thalassaemia]. 197 69

A total of 72 chromosomes from 36 Indonesian patients, 23 with beta-thalassemia major and 13 with Hb E-beta-thalassemia, were analyzed by specific oligonucleotide hybridization after DNA amplification. Thirteen had the beta E mutation (codon 26 GAG----AAG). Of the 59-beta-thalassemic chromosomes, 32 were of the variant IVS-1 nt5 (G----C). Seven had the mutation IVS-2 nt654 (C----T), one had the mutation codon 41/42 (deletion CTTT), and one had the mutation codon 17 (AAG----TAG). Another six with the mutation IVS-1 nt1 (G----T), one with the mutation IVS-1 nt1 (G----A), four with the mutation codon 15 (TGG----TAG), one with a mutation codon 30 (AGG----ACG), and one with a mutation codon 35 (deletion C) were first identified by direct sequencing of a patient's genomic DNA followed by further hybridizing other patients' DNA with the appropriate oligonucleotide probes. Five did not carry the common mutations previously described in Asian populations. The four most prevalent mutations encountered made up 83% of the total number of beta-thalassemic chromosomes studied. The most common mutation, IVS-1 nt5 (G----C), was mostly associated with two different haplotypes.
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PMID:Beta-thalassemia mutations in Indonesia and their linkage to beta haplotypes. 258 24

beta-Thalassaemia major patients have chronic anaemia and since 3-4 per cent of Singaporeans carry the beta-gene, prenatal diagnosis is essential. We evaluated the amplification refractory mutation system (ARMS) technique as a routine test for prenatal diagnosis of beta-major. Six mutations along the beta-gene were studied--41-42 (-TCTT), IVSII #654 (C-T), 17 beta (A-T), -28 TATA (A-G), IVSI #5 (G-C), and IVSI #1 (G-T). Our results indicate that prenatal diagnosis using these mutations can be offered to 90 per cent (35/39) of our Chinese couples and 54.6 per cent (12/22) of our Malay couples at risk. Confirmation of ARMS results was carried out using allele-specific oligonucleotide hybridization. Prenatal diagnosis using ARMS was successfully carried out in nine cases which included a set of triplets and twins. The triplets were diagnosed with the beta-trait carrying the 41-42 mutation. The couple with twins possessed the #654 mutation and one twin was diagnosed with the beta-trait and the other with #654 homozygosity. Genomic sequencing of the undefined mutations in the Chinese couples revealed rarer mutations at -29 and an ATG-AGG base substitution at the initiation codon for translation. In the Malay couples, genomic sequencing detected mutations at codon 15 (TGG-TAG) and codon 26 (GAG-AAG). We conclude that ARMS with its direct detection of amplified products by gel electrophoresis provides an accurate, rapid, and simpler method for our beta-thalassaemia prenatal diagnosis programme in Singapore.
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PMID:The amplification refractory mutation system (ARMS): a rapid and direct prenatal diagnostic technique for beta-thalassaemia in Singapore. 787 57

The mutations producing beta-thalassemia minor in 227 Taiwanese were studied using the method of naturally and amplified created restriction sites. beta-Thalassemia minor was caused by one beta-globin gene mutation in most of the cases (225/227); only a few cases were caused by two gene mutation (2/227). The most common type of mutation was frameshift codon 41/42 (-TCTT) (93/227), followed in descending order by the C-->T substitution at nucleotide 654 of IVS-2 (83/227), the nonsense mutation A--T at codon 17 (22/227), the A-->T mutation at position -28 of the promotor region (12/227), the frameshift codon 27/28 (+C) (6/227), the initial codon mutation (ATG-->AGG) (5/227), and one each of the codon 71/72 (+A), IVS-1 nt 1 (G-->T), IVS-1 3' end (TAG-->GAG), and nonsense codon 43. In the two cases of the two-gene mutation, one was the nt 654 mutation with Hb Kaohsiung and another one was frameshift codon 41/42 with Hb Meinung. The first four mutations accounted for more than 90% of the mutations. The C-->T substitution at the nt 654 of IVS-2 and initial codon mutation in our study had a higher incidence than in other Southeast Asia areas. Comparison of clinical data in different types of beta-thalassemia showed that there were higher MCV and MCH levels in beta (+)-thalassemia.
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PMID:Molecular basis of beta-thalassemia minor in Taiwan. 808 20

We have systematically analyzed beta-thalassemia genes using polymerase chain reaction-related techniques, dot-blot hybridization with oligonucleotide probes, allele specific-polymerase chain reaction, and sequencing of amplified DNA fragments from 41 unrelated patients, including 37 beta-thalassemia homozygotes, three with beta-thalassemia/Hb E, and one with beta-thalassemia/Hb S. Four different beta-thalassemia mutations were detected in 78 alleles. These are the IVS-I-5 (G-->C), codon 30 (AGG-->ACG) [also indicated as IVS-I (-1)], IVS-I-1 (G-->A), and codons 41/42 (-TTCT) mutations. The distribution of the beta-thalassemia mutations in the Maldives is 58 alleles (74.3%) with the IVS-I-5 (G-->C) mutation, 12 (15.4%) with the codon 30 (AGG-->ACG) mutation, seven (9%) with the IVS-I-1 (G-->A) mutation, and one with the codons 41/42 (-TTCT) mutation. The first three mutations account for 98.7% of the total number of beta-thalassemia chromosomes studied. These mutations are clustered in the region spanning 6 bp around the junction of exon 1 and the first intervening sequence of the beta-globin gene. These observations have significant implications for setting up a thalassemia prevention and control program in the Maldives. Analysis of haplotypes and frameworks of chromosomes bearing each beta-thalassemia mutation suggested that the origin and spread of these mutations were reflected by the historical record.
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PMID:Molecular basis of beta-thalassemia in the Maldives. 957 31

The beta thalassemia alleles in 53 thalassemic Indo-Mauritian patients and their families consisting of 23 homozygous beta-thalassemia, 9 HbE/beta-thalassemia, 18 HbS/beta-thalassemia, 1 HbD/beta-thalassemia, 1 deltabeta/beta-thalassemia and 1 HbH/beta-thalassemia from the island of Mauritius were studied. Characterization by polymerase chain reaction-based reverse dot blot hybridization technique revealed that the IVS1-5 (G-->C) mutation accounted for 74% of the beta thalassemic alleles, while six other mutations occurred at much lower frequencies: HbE codon 26 (G-->A); 10.4%, codon 8/9 (+G); 3.5%, codon 30 (AGG-->ACG) also called IVSI (-1).G-->C; 3.5%, codon 15 (G-->A); 3.5%, codon 41/42 (-CTTT); 2.4% and -28 (A-->G); 2.4%. Association of these mutations to specific beta globin gene sequence framework and haplotype allowed to trace their ancestral link. These data are useful in future molecular screening of the population in view of implementing a thalassemia prevention and control program in Mauritius.
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PMID:Spectrum of beta thalassemia mutations and their linkage to beta-globin gene haplotypes in the Indo-Mauritians. 1107 47

Molecular characterization and prenatal diagnosis for beta-thalassemia can be carried out using the Amplification Refractory Mutation System (ARMS). The ARMS is a rapid and direct molecular technique in which beta-thalassemia mutations are visualized immediately after DNA amplification by gel electrophoresis. In the University of Malaya Medical Center, molecular characterization and prenatal diagnosis for beta-thalassemia is carried out using ARMS for about 96% of the Chinese and 84.6% of the Malay patients. The remaining 4% and 15.4% of the uncharacterized mutations in the Chinese and Malay patients respectively are detected using DNA sequencing. DNA sequencing is an accurate technique but it is more time-consuming and expensive compared with the ARMS. The ARMS for the rare Chinese beta-mutations at position -29 (A-->G) and the ATG-->AGG base substitution at the initiator codon for translation in the beta-gene was developed. In the Malays, ARMS was optimized for the beta-mutations at codon 8/9 (+G), Cap (+1) (A-->C) and the AATAAA-->AATAGA base substitution in the polyadenylation region of the beta-gene. The ARMS protocols were developed by optimization of the parameters for DNA amplification to ensure sensitivity, specificity and reproducibility. ARMS primers (sequences and concentration), magnesium chloride concentration, Taq DNA polymerase and PCR cycling parameters were optimized for the specific amplification of each rare beta-thalassemia mutation. The newly-developed ARMS for the 5 rare beta-thalassemia mutations in the Chinese and Malays in Malaysia will allow for more rapid and cost-effective molecular characterization and prenatal diagnosis for beta-thalassemia in Malaysia.
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PMID:The use of the amplification refractory mutation system (arms) in the detection of rare beta-thalassemia mutations in the Malays and Chinese in Malaysia. 1204 67

Beta-Thalassemia is uncommon in the Korean population, however, it must be considered in the differential diagnosis of hypochromic anemia. The molecular characterization of beta-thalassemia is absolutely necessary for molecular diagnosis as well as any genetic epidemiological study in this region. We analyzed the molecular basis of beta-thalassemia in 38 Korean families. Using direct sequencing of genomic DNA amplified through polymerase chain reaction and haplotype analysis, 35 beta-thalassemic genes were characterized, all of which were heterozygous. Twelve different mutations were identified. The most common mutations noted included the initiation codon ATG-->AGG (beta0) (28.9%), codon 17 (beta0) (A-->T) (18.4%), and IVS-II-1 (beta0) (G-->A) (10.5%). Interestingly, mutations causing dominantly inherited beta-thalassemia were also common (15.7%). All four cases with the IVS-II-1 (G-->A) mutation were linked to the silent mutation of codon 91 (C-->T) of the beta-globin gene. The initiation codon A7G-->AGG and IVS-II-1 (G-->A) with codon 91 (C-->T) mutations were found in the Far East only, and may be inherited from a common origin for each mutation, at least in Koreans. The codon 17 (A-->T) and codons 41/42 (beta0) (-TTCT) were suggested to be introduced by gene-flow from southern China. Otherwise, only Hb Korea [codons 33/34 (beta0) (-GTG)] and a novel beta-thalassemic mutation, codons 89/90 (beta0) (-GT), were identified in Koreans. This mutation spectrum is characteristic of the low prevalence area of beta-thalassemia in Korea, it is, however, quite different from the adjacent countries, Japan and China.
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PMID:Beta-thalassemia in the Korean population. 1214 56

Korea is in the low-prevalence area of beta-thalassemia and the Korean population has relatively homogenous racial characteristics. Recently, we identified some causative mutations of the Korean beta-thalassemia patients. In order to elucidate the genetic background of beta-thalassemia alleles in Koreans, we determined the restriction fragment length polymorphism (RFLP)-haplotype and framework (FW) in nine beta-thalassemia chromosomes of five different causative mutations by PCR-based method and family linkage study. The result that the haplotype and the framework linked to the initiation codon ATG-->AGG mutation were -+-++-+ and FW3A, respectively, in all of three families in this study suggests a common origin of this mutation at least in Koreans. A novel beta-thalassemia mutation, codons 89/90 -TG, showed discrepancy between -++--++- and FW1, which could be explained by gene conversion. A case of codons 8/9 +G frameshift mutation had +----++ and FW1. The linkage of the two beta-thalassemia mutations, codon 17 AAG-->TAG and codons 41/42 -TTCT, with specific haplotypes and frameworks common to the Koreans and the neighboring countries suggests that those mutations are influenced by the genetic flow from the south China.
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PMID:RFLP haplotypes of beta-globin gene complex of beta-thalassemic chromosomes in Koreans. 1217 41

Beta-thalassemia is uncommon in the Korean population, however it must be considered in the differential diagnosis of hypochromic anemia. The molecular characterization of beta-thalassemia is absolutely necessary for molecular diagnosis as well as any genetic epidemiological study in this region. We analyzed the molecular basis of beta-thalassemia in 47 Korean families. Using direct sequencing of genomic DNA amplified through PCR and haplotype analysis, 44 beta-thalassemia genes were characterized, all of which were heterozygous. Fourteen different mutations were identified. The common mutations noted included the initiation codon (CD) ATG-->AGG (23.4%), CD 17 A-->T (21.2%), and IVS-II-1 G-->A (12.7%). Interestingly, mutations causing dominantly inherited beta-thalassemia were common (17.0%). All cases of IVS-II-1 G-->A mutations were linked to the silent mutation of CD 91 C-->T of the -globin gene. The initiation CD ATG-->AGG and IVS-II-1 G-->A with CD 91 C-->T were found in the Far East only, and may be inherited from a common origin for each mutation, at least in Koreans. CD17 A-->T and CDs 41/42-TTCT were suggested to be introduced by gene-flow from southern China. Otherwise, Hb Korea, CDs 89/90 -GT and a novel beta-thalassemia mutation, CD 131 CAG-->TAG, were only identified in Koreans. This mutation spectrum is characteristic of the low prevalent area of beta-thalassemia, however it is quite different even from the adjacent countries, Japan or China.
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PMID:Beta-thalassemia in the Korean population. 1243 Sep 7


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