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 present report described the hematologic and molecular study of the second case of Hb D-Punjab associated with a beta zero-thalassemia found in Spain and the first case in which the mutations have been identified at molecular level. A family from India is studied, which is constituted by mother (I2) and 3 children (II1, II2 and II3). The molecular characterization of the hemoglobinopathy was made by electrophoretic and chromatographic techniques and confirmed by sequencing of the beta-globin gene. The mutation causer of the beta-thalassemia was studied by PCR-ARMS. The mother (I2) and one of her child (II2) are carriers of the gene for beta zero-thalassemia owing to the frameshift CD 8/9 mutation (+ G). Other of them (II1) is heterozygous for Hb D-Punjab without beta-thalassemia association. The third child (II3) knows a double heterozygote state for Hb D-Punjab/beta zero-thalassemia (hemoglobin D-thalassemia). In spite of the patient with hemoglobin D-thalassemia has 94.5% of Hb D, without Hb A, the hematologic picture belongs to thalassemia trait with moderate haemolytic anemia, intense microcytosis and hypochromia and numerous target cells. This hematologic picture discloses the mildness of the Hb D-Punjab, but the reliable responsible for the phenotype is the disbalance in the synthesis of globin chains, because of frameshift CD 8/9 mutation (+ G) beta zero-thalassemia mutation.
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PMID:[The association of beta zero-thalassemia and Hb D Punjab in a family of Indian origin. The second case reported in Spain]. 913 46

The distribution of variant hemoglobin in India has been related to various ethnic groups among other factors. beta-Thalassemia is the most frequent monogenic disorder in the country. Analysis of hemoglobin of 435 cases from Eastern India was performed by electrophoresis and by other quantitative methods. Analysis of the beta-globin gene of 112 cases used ARMS (amplification refractory mutation system)-PCR (polymerase chain reaction) techniques showing that IVS-1 nt 5 (G-->C) is the most prevalent mutation in populations from Eastern India. IVS-1 nt 5 (G-->C) interacts with the codon 26 (G-->A) mutation to produce E beta-thalassemia phenotype in the samples from West Bengal, India.
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PMID:The occurrence of beta-thalassemia mutation and its interaction with hemoglobin E in the eastern India. 922 Jun 58

We screened 110 DNA samples from carriers of beta-thalassaemia, using the ARMS-PCR technique with primers for common Mediterranean mutations. Unidentified samples were subjected to a heteroduplex analysis with Universal Heteroduplex Generators covering the beta-globin gene, followed by DNA sequencing. In total, 16 different mutations were detected, the most frequent being IVSI-110 (40%), followed by other common Mediterranean mutations (IVSI-1, IVSII-1, IVSI-6). Other mutations detected were of Lebanese, Turkish, Iranian, Kurdish, Bulgarian and Asian Indian origin. The most heterogeneous religious group seems to be the Sunni Muslims, with 13 mutations, while only 2 mutations were detected among the Christian Maronites. Results from this study are compared with those from other Mediterranean and neighbouring countries.
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PMID:The spectrum of beta-thalassaemia mutations in the Lebanon. 935 11

Among 365 carriers of beta-thalassemia, 13 subjects remained uncharacterized after ARMS analysis. Among these 13 individuals, 8 mutations were identified by direct sequencing of the PCR-amplified product, which have not been described in Asian Indians earlier. These included (1) T-C substitution at IVS II position 591, a new beta-thalassemia mutation which probably creates an alternative donor splice site in antisense strand; (2) the mutations CoD4 (T-A), CoD5 (C-T), CoD6 (G-T) at cis location; (3) CoD13 (C-T), CoD26 (G-A), CoD 27/28(-C) at cis location; (4) CoD 8 (A-G); (5) CoD30 (G-C); (6) CoD5 (-CT); (7) IVSI-1 (G-A); and (8) FS47/48 (+ATCT). The latter four have been described in other populations but are identified in Asian Indians for the first time. This completes the characterization of beta-thalassemia mutations in 365 carriers of Asian Indian origin, enabling us to provide a comprehensive prenatal diagnosis of beta-thalassemia in our population.
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PMID:Rare beta-thalassemia mutations in Asian Indians. 1107 64

Beta-thalassemia major patients have chronic anemia and are dependent on blood transfusions to sustain life. Molecular characterization and prenatal diagnosis of beta3-thalassemia is essential in Malaysia because about 4.5% of the population are heterozygous carriers for beta-thalassemia. The high percentage of compound heterozygosity (47.62%) found in beta-thalassemia major patients in the Thalassaemia Registry, University of Malaya Medical Centre (UMMC), Malaysia, also supports a need for rapid, economical, and sensitive protocols for the detection of beta-thalassemia mutations. Molecular characterization of beta-thalassemia mutations in Malaysia is currently carried out using ARMS, which detects a single beta-thalassemia mutation per PCR reaction. We developed and evaluated Combine amplification refractory mutation system (C-ARMS) techniques for efficient molecular detection of two to three beta-thalassemia mutations in a single PCR reaction. Three C-ARMS protocols were evaluated and established for molecular characterization of common beta-thalassemia mutations in the Malay and Chinese ethnic groups in Malaysia. Two C-ARMS protocols (cd 41-42/IVSII #654 and -29/cd 71-72) detected the beta-thalassemia mutations in 74.98% of the Chinese patients studied. The CARMS for cd 41-42/IVSII #654 detected beta-thalassemia mutations in 72% of the Chinese families. C-ARMS for cd 41-42/IVSI #5/cd 17 allowed detection of beta-thalassemia mutations in 36.53% of beta-thalassemia in the Malay patients. C-ARMS for cd 41-42/IVSI #5/cd 17 detected beta-thalassemia in 45.54% of the Chinese patients. We conclude that C-ARMS with the ability to detect two to three mutations in a single reaction provides more rapid and cost-effective protocols for beta-thalassemia prenatal diagnosis and molecular analysis programs in Malaysia.
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PMID:Combine-ARMS: a rapid and cost-effective protocol for molecular characterization of beta-thalassemia in Malaysia. 1133 96

Analysis of the molecular basis of hemoglobinopathies provides an opportunity to define genotype-phenotype variations as well as establish the origin of mutation. The present study deals with a large cohort of 1,661 cases referred to the counseling unit and 889 individuals from random screening of the population of Tripura. Characterization of mutation in 291 cases (582 alleles) was performed by the PCR-ARMS method using genomic DNA. The haplotype of 56 beta(E) mutation-bearing chromosomes were identified by the RFLP-PCR method. Genotypes were constructed and correlated with hematological and clinical phenotypes. IVS-1nt 5 (G-->C) mutation was observed as the most frequent mutation, followed by codon 30 (G-->C). Production of HbE was significantly (P < 0.001) higher in nontransfusion-dependent Ebeta-thalassemia patients. beta(E) mutation was observed only on four haplotypes linked to framework 2. Type 2 haplotype was observed mainly from chromosomes of Tripura origin, but none from South Bengal. Homozygous E individuals with 1//1 genotype were significantly (P < 0.01) more anemic compared to individuals with 2//2 genotype. This work creates a database of hemoglobinopathy mutations for the population of Eastern India which will facilitate prenatal diagnosis and counseling. Am. J. Hum. Biol. 12:454-459, 2000. Copyright 2000 Wiley-Liss, Inc.
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PMID:Interaction of different hemoglobinopathies in Eastern India with a view to establish genotype-phenotype correlation. 1153 36

The inherited disorders of hemoglobin represent the most common Mendelian disease worldwide, with a higher prevalence among Mediterraneans, Asians, Africans, and Indians. Altered beta-globin sequences, causing either hemoglobinopathies or beta-thalassemia syndromes, are due to more than 200 different mutations in the beta-globin gene. Prevention programs based on postnatal and prenatal molecular diagnosis of heterozygous carriers and/or patients require the use of reliable mutation scanning methods in at-risk populations. We have developed a rapid and highly specific mutation screening test based on the denaturing high-performance liquid chromatography (DHPLC) system. The sensitivity and specificity of the method were tested on the full genomic region of the beta-globin gene in 30 normal Italian subjects and 40 heterozygous carriers in which 25 different beta-globin mutations had been previously characterized by multiplex-ARMS technique. The results showed DHPLC to be 100% sensitive and specific. All the 25 sequence alterations and two previously undetected polymorphisms were precisely identified with neither false positive nor false negative results. In addition, 12 compound heterozygous and four homozygous patients were successfully subjected to DHPLC. Overall, the method was able to rapidly identify the most common beta-globin mutations, accounting for more than 97% of beta-globin alleles in the Italian population. Compared to classical approaches of mutation screening, this method allows a rapid, highly sensitive, cost-effective, and semi-automated simultaneous mutational scanning of a large number of samples.
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PMID:Reliability of DHPLC in mutational screening of beta-globin (HBB) alleles. 1185 46

In Vietnam, the carrier rate for beta-thalassemia varies from 1.5% to 25% depending on the ethnic groups of the population. The molecular basis of beta-thalassemia in South Vietnam was studied in 50 unrelated beta-thalassemia patients. Of these, 31 had beta-thalassemia/Hb E, 18 were homozygous for beta-thalassemia, and 1 carried the beta-thalassemia trait. The majority of the patients were Kinh, four were Chinese, and two were Kinh-Chinese. All had severe anemia and received blood transfusions regularly, every 1-3 months. Hepatosplenomegaly was found in all patients, and splenectomy had been done in six patients. Normal alpha-globin genotype (alpha alpha/alpha alpha) was found in all subjects. Reverse dot-blot hybridization using oligonucleotide probes specific for Southeast Asian mutations can detect beta-thalassemia in 60 chromosomes in addition to 31 chromosomes with beta(E) mutation. Excluding the beta(E) gene, six previously reported Thai and Chinese beta-thalassemia mutations were found, including codons 41/42 (-TCTT) 35.3%, codon 17 (A-->T) 25.0%, -28 (A-->G) 7.3%, codons 71/72 (+A) 7.3%, IVS-II nt 654 (C-->T) 7.3%, and IVS-I nt 1 (G-->T) 6.0%. The Vietnamese frameshift mutation at codon 95 (+A) was detected by ARMS in seven chromosomes (10.3%). DNA polymorphism of the beta-globin gene cluster carrying the codon 95 mutation was - + - - - - - + for (G)gamma/XmnI, epsilon/HincII, (G)gamma/HindIII, (A)gamma/HindIII, psi beta/HincII, 3' psi beta/HincII, beta/AvaII, and 3'beta/BamHI, respectively. The remaining mutation detected by the gap PCR was a large deletion known as the Chinese (G)gamma((A)gamma delta beta)(0)-thalassemia. The two most common mutations were the frameshift at codons 41/42 (-TCTT) and the nonsense mutation in codon 17 (A-->T). Thus beta-thalassemia mutations in South Vietnam is similar to the previous report from the North, although at different frequencies. This result will help to establish a center for prenatal diagnosis and for prevention and control of thalassemia in Vietnam.
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PMID:Molecular analysis of beta-thalassemia in South Vietnam. 1235 5

At present, the application of combined methods in molecular biology allows us to carry out the prenatal diagnosis in a more rapid and less onerous manner especially when the family presents an index case. In this study, we have analyzed a family with one case of intermediate beta-thalassemia. First, we have used the denaturing gradient gel electrophoresis (DGGE). Then, we have identified the mutations by the refractory mutation system technique (ARMS PCR) using specific primers for the most frequent mutations in the Tunisian population (codon 39 (C --> T) and IVS-I-2 (T--> G) for beta0 thalassemias and IVS-I-110 (G --> A) for beta+ thalassemias). The analyzed family has shown the IVS-I-110 (G --> A) mutation in the heterozygous state in the mother and the index case. Subsequently, sequencing in the gene revealed a frameshift 8 (-AA) mutation in the father and his daughter. This patient is thus a compound heterozygote Codon 8 (-AA)/IVS-I-110. DGGE and ARMS PCR analysis of foetal DNA extracted from trophoblast culture didn't show any of the two mutations found in the family.
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PMID:[Diagnostic strategy of beta-thalassemic mutation in a Tunisian family, application in prenatal diagnosis]. 1270 81

Hb H disease is generally associated with moderate to severe anemia but rarely requires regular blood transfusion. We recently studied two apparently unrelated patients with transfusion-dependent Hb H disease. Hemoglobin studies demonstrated Hb H and Hb Bart's without other detectable abnormal globin species. Extensive molecular analyses of the alpha globin genes and their regulatory sequence (HS-40) revealed that both patients are compound heterozygotes for alpha0 thalassemia (--(SEA)) and a novel point mutation, a thymidine insertion after codon 131 of the alpha1 gene. The resulting frameshift gives rise to a highly unstable alpha globin chain, which we refer to as "Hb Pak Num Po," containing an additional 34 amino acids. This unusual alpha1 globin variant clearly causes alpha thalassemia, but the unexpectedly severe phenotype suggests that this mutation may have additional effects on red cell physiology. A PCR-based (ARMS) assay was developed for rapid detection of this novel mutation, and this might be useful to study the prevalence of this novel mutation which poses potentially significant clinical consequences in populations of Southeast Asia. Detecting carriers of this mutation using the molecular diagnostic procedures described will provide the means to screen and prevent a potentially severe form of alpha thalassemia in Thailand.
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PMID:Co-inheritance of Hb Pak Num Po, a novel alpha1 gene mutation, and alpha0 thalassemia associated with transfusion-dependent Hb H disease. 1497 97


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