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)

Hb Johnstown [beta109(G11)Val-->Leu], a high oxygen affinity hemoglobin (Hb) variant associated with beta0-thalassemia (thal) [IVS-I-1 (G-->A)], was identified in an 8-year-old girl referred to our laboratory because of erythrocytosis and a left-shifted oxygen dissociation curve (ODC). The phylogenetic tree showed that the mother was heterozygous for the Hb variant and the father was a beta0-thal carrier. This Hb variant, with normal electrophoresis, was characterized at the DNA level by beta gene sequencing. The amino acid substitution potentially disrupts alpha1beta1 contacts i n the deoxyHb conformation, thus shifting the equilibrium towards the high affinity oxyHb conformation. The erythrocytosis and low values for actual P50 due to Hb Johnstown were more marked due to the co-inheritance of the beta0-thal.
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PMID:Hb Johnstown [beta109(G11)Val-->Leu]: A high oxygen affinity variant associated with beta0-thalassemia. 1565 89

This study reports the molecular characterization of thalassemia syndromes in Serbian and Montenegrin populations. We identified eight beta-thalassemia mutations [codon 39 (C-->T), IVS-I-110 (G-->A), IVS-II-745 (C-->G), codon 44 (-C), -87 (C-->G), IVS-II-1 (G-->A), IVS-I-6 (T-->C), IVS I-1 (G-->A)] in 70 members of 29 families using polymerase chain reaction, reverse dot blot, amplification refractory mutation system and direct sequencing analysis. Hemoglobin (Hb) Lepore was found to be the most common cause of the thalassemia phenotype. Hb Sabine and alpha-thalassemia were detected as well. We also studied beta-globin gene cluster haplotypes and their association with the most common mutations. A novel haplotype associated with the Hb Lepore gene was identified. The results presented herein allowed the implementation of a prenatal diagnosis program in Serbia and Montenegro.
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PMID:Molecular basis of thalassemia syndromes in Serbia and Montenegro. 1587 Apr 87

beta-Thalassemia (thal) is an autosomal recessive disorder that results in hypochromic hemolytic anemia in affected patients. In the West Bank area of Palestine, the prevalence of beta-thal trait is approximately 3.5% among the population, with an estimated 120,000 carriers. Seventeen beta-globin gene mutations could be identified in 148 patients using polymerase chain reaction (PCR), amplification refractory mutation system (ARMS)-PCR and direct sequencing. The predominant mutations included: IVS-I-6 (T --> C) (28.7%), IVS-I-110 (G --> A) (17.6%), codon 37 (G --> A) (10.4%), IVS-I-1 (G --> A) (9%), codons 106/107 (+ G) (6.8%) and codon 39 (C --> T) (4.6%). Other less frequent and rare mutations included: IVS-II-1 (G --> A), codon 5 (-CT), IVS-II-848 (C --> A), -30 (T --> A), codons 8/9 (+ G), IVS-I-5 (G --> C), -28 (A --> C), IVS-II-745 (C --> G), codon 6(-A), codon 27 (G --> T) and codon 30 (AGG --> ACG). Most patients (62.2%) were homozygous for one type of mutation, while the rest (27.3%) were compound heterozygotes. Some patients were heterozygous for beta-thal and sickle cell anemia traits. No mutations could be detected in both alleles of eight patients, while in seven patients only one mutant allele could be detected. Further investigations are needed to resolve the corresponding genotypes of these patients. This study represents a comprehensive investigation of the type, frequency, and distribution of thalassemia mutations among the Palestinian population in the West Bank region of Palestine. A degree of similarity and significant variations was evident in the type and frequency of mutations when the present mutations profile was compared with similar ones among various Arab and non Arab populations. The association between the identified mutations and the corresponding genotypes of our patients with specific polymorphism frameworks in the beta-globin gene was performed and the results revealed linkage disequilibrium.
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PMID:Spectrum of beta-globin gene mutations among thalassemia patients in the West Bank region of Palestine. 1592 Nov 64

We report on three previously undescribed unstable hemoglobin (Hb) variants: Hb Miami, Hb Hershey and Hb Abington. Hb Miami was associated with a beta(+)-thalassemia (thal) mutation [IVS-I-110 (G-->A)], whereas Hb Hershey was associated with a B0-thal mutation [IVS-I-1 (G-->A)]. Hb Hershey also has decreased oxygen affinity. These three Hb variants illustrate the range of clinical severity that can be seen with unstable Hb variants, particularly when combined with a thalassemic mutation.
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PMID:Two unstable beta chain variants associated with beta-thalassemia: Hb Miami [beta116(G18)his-->Pro], and Hb Hershey [beta70(E14)Ala-->Gly], and a second unstable Hb variant at 170: Hb Abington [beta70(E14)Ala-->Pro]. 1637 Apr 83

Thalassaemia is a group of inherited haemoglobin disorders characterized by reduced synthesis of one or more of the globin chains leading to imbalanced a /non-a globin synthesis which is the major factor in determining the severity of the disease in the thalassaemia syndromes. In Egypt, beta-thalassemia is the commonest cause of chronic haemolytic anaemia and it represents a major genetic disease and a public health problem. This study included 50 transfusion dependent beta-thalassaemic cases. They were subjected to detailed history taking, physical examination to assess the size of liver and spleen and laboratory investigations including complete haemogram, bone marrow (BM) aspiration, haemoglobin electrophoresis and serum ferritin. Genetic analysis for detection of point mutations was done by PCR amplification refractory mutation system (ARMS) which is a PCR method based on allele specific priming. Using this technology, it was possible to characterize mutations in 73% of beta-thalassaemia cases, while 27% remained uncharacterized. The five common mutations used were: IVS-1-110 (G-->A), IVS-1-6 (T-->C) IVS-I-1 (G-->T), IVS-II-1 (G-->A) and codon 39 (C-->T). The commonest was IVS-I-110 (62%) followed by IVS-1-6 (7%), then IVS-I-1 (4%). On the other hand mutations such as IVS-II-1 and Cd- 39 were not found in any of our patients. No significant difference was found between different genotypes regarding the frequency of blood transfusion needed, degree of anaemia and microcytosis, HbF% or serum ferritin levels. This may be due to the small sample size of some of the genotypes (IVS-I-110/IVS-I-1 & IVS-I-110/IVS-I-6) or due to repeated blood transfusions which mask the patient original CBC and Hb electrophoresis pattern or due to co-inheritance of other genetic modifying factors that alter the typical phenotype.
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PMID:Molecular basis of beta-thalassemia in Alexandria. 1673 35

Beta thalassemia minor phenotypes with normal HbA2 levels and decreased MCV and MCH values are relatively rare beta-thalassemia traits. Here, we describe a case with normal HbA2 and decreased MCV and MCH level. Amplification refractory mutation system-polymerase chain reaction(ARMS-PCR) revealed IVS I-1 (G-->T) mutation in the beta-globin gene. Direct sequencing of the delta-globin gene revealed a previously reported Hb variant called Hb A2 Etolia (Gene Bank Accession No. DQ106871). This is the first case reporting HbA2 Etolia in association with the beta-IVS I-1 (G-->T) mutation in Iran. Reduced HbA2 expression by a co-inherited HbA2 variant resulting in decreased HbA2, in Cis or Trans, may cause problems in carrier diagnostics and eventually in genetic counseling and prenatal diagnosis when insufficient molecular analyses are performed.
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PMID:First report on the co-inheritance of (beta) IVS I-1 (G-->T) Thalassemia with the (gamma) CD85 [Phe-->Ser (F1) (TTT-->TCT)] HbA2 Etolia in Iran. 1678 21

beta-Thalassemia (thal) is an important health problem in the Dohuk region of northern Iraq because of its high carrier rate and the frequency of consanguineous marriages. Thus, the need to establish an effective preventative program is paramount. As part of this effort, we initiated this study to determine the molecular basis of this disorder in the region. For the latter purpose, either parent of 104 registered beta-thal major/intermedia patients had their full blood counts, hemoglobin (Hb) electrophoresis, Hb A2 and Hb F quantitation performed. Their DNA was extracted, amplified and reverse hybridized to specific oligonucleotide probes to detect 20 beta-thal mutations. The testing detected 12 beta-thalassemic mutations. The eight most frequent were: IVS-II-1 (G-->A), codon 44 (-C), codon 5 (-CT), IVS-I-1 (G-->A), codon 39 (C-->T), IVS-I-6 (T-->C), codons 8/9 (+G) and IVS-I-5 (G-->C). These mutations accounted for 81.7% of the thalassemic defects in the studied individuals. The less frequent mutations were: codon 8 (-AA), IVS-I-110 (G-->A), codon 30 (G-->C) and codon 22 (-7 bp), and the beta-thalassemic defects remained uncharacterized in 11.5% of cases. This is the first study of beta-thal mutations from Iraq, and shows a frequency of thalassemic defects different from those reported in surrounding countries. It provides a foundation for prenatal genetic testing that will be part of a thalassemia prevention program in the Dohuk region.
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PMID:Molecular characterization of beta-thalassemia in the Dohuk region of Iraq. 1698 3

This paper summarizes the results on the epidemiology and molecular basis of thalassemias and other hemoglobinopathies in the Republic of Macedonia. Over the past 40 years, population surveys of more than 22,000 participants (school children and workers) from all over the country, have shown that the average incidence of beta-thalassemia (thal) trait is 2.6%, ranging from less than 1% in the northeast to 10% in the south. The frequency of deltabeta-thal is 0.2%, while the frequency of the Swiss type of hereditary persistence of fetal hemoglobin (HPFH) is 0.3%. Screening of 9,619 newborns has shown that the frequency of alpha-thal trait is 1.5%, of which alpha-thal-2 is 1.45% and alpha-thal-1 is 0.05%. The molecular basis of the different forms of beta-thal and other hemoglobinopathies has been completely defined. Among the Macedonians, over 450 beta-thal chromosomes have been studied. Fifteen different beta-thal mutations have been detected, four of which [IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-I-1 (G-->A), codon 39 (C-->T)] account for 85% of all beta-thal chromosomes. Among the Albanians, 48 beta-thal chromosomes have been studied. Eight different mutations have been detected, four of which [codon 39, -30 (T-->A), IVS-I-110, IVS-I-1] account for 85% of all beta-thal chromosomes. Four new mutations [-101 (C-->A), -87 (C-->G), -30, polyadenylation signal (poly A) (AATAAA-->AATGAA)] have been characterized. Molecular analyses of DNA from over 20 unrelated cases with deltabeta-thal have shown that this condition is caused by a 13 kb deletion (Sicilian type); in two families a deletion of 18 to 23 kb (Macedonian type of deltabeta-thal) was discovered. Molecular analyses of alpha-thal in the Republic of Macedonia have shown the following types of molecular defects: 20.5 kb deletion, 17.5 kb deletion, 3.7 kb deletion, poly A mutation (AATAAA-->AATGAA), and Hb Icaria [alpha142, Term-->Lys, TAA-->AAA (alpha2)]. The incidence of abnormal hemoglobins (Hbs) in the Republic of Macedonia is 0.4%. Three different alpha chain variants among 10 families, seven different beta chain variants among 33 families, two gamma chain variants in two newborns, one variant with an extended alpha chain, and Hb Lepore among 105 families, have been observed. Structural analysis of numerous cases with Hb Lepore showed that the variant was of the Washington-Boston type.
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PMID:Thalassemias and other hemoglobinopathies in the Republic of Macedonia. 1736

beta-Thalassemia (thal) is the most common recessive inherited disorder in Mediterranean populations. It is estimated that the frequency of this disease in the Moroccan population is between 1.5 and 3.0%. Severe forms of homozygous thalassemia cases require expensive and technically demanding curative (bone marrow transplantation) or palliative (chronic transfusion/chelation) therapies. The -158 (C-->T) polymorphism of the (G)gamma-globin gene (XmnI polymorphism) is known to ameliorate the severity of the disease because of it strong association with an increased production of fetal hemoglobin (Hb F). Among the many known mutations in Morocco, six are common [codon 39 (C-->T), frameshift codon (FSC) 8 (-AA), IVS-II-745 (CG), FSC 6 (-A), -29 (A-->G) and IVS-I-1 (G-->A)]. In this study, we have investigated, in 82 Moroccan beta-thalassemic chromosomes, the correlation between the six common mutations and the XmnI polymorphism using the Fisher exact test. The XmnI polymorphism was divided into two categories, (XmnI [+] and XmnI [-]) and the six common Moroccan mutations into two groups (group I with FSC 8 and group II without FSC 8). Correlation was carried out between the XmnI [+] category and the six common mutations individually that showed that 68% of chromosomes in the XmnI [+] category had the FSC 8 (-AA) mutation. The results reported here show that there is a positive correlation between the XmnI polymorphism and FSC 8 mutation in linkage with haplotype IV [- + - + + - +] (p <10(-5)). In conclusion, molecular determination of genetic markers in early childhood will help to identify candidates for pharmacological Hb F switching by hydroxyurea (HU). In the Moroccan population, a good response to HU treatment should be suspected in cases with the -158 (C-->T) polymorphism in linkage with haplotype IV and internal beta-globin gene framework 3.
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PMID:Genotypic correlation between six common beta-thalassemia mutations and the XmnI polymorphism in the Moroccan population. 1748 95

Genetic and acquired disorders that foster a procoagulable state represent risk factors for stroke in childhood. Although an increased incidence of thromboembolic complications has been reported in patients with thalassemia, severe cerebral thromboembolism has rarely been observed in patients with beta-thalassemia minor. This article describes a case study of a 1-year-old boy who presented with left-sided hemiparesis, seizures, microcytic anemia, and recent infection with reactive thrombocytosis. Ischemic infarction in the territory of the right middle cerebral artery was confirmed by magnetic resonance imaging and magnetic resonance angiography. Genetic tests showed that the patient was heterozygous for the beta(degrees) -thalassemia IVS-I-1 mutation and homozygous for the methylentetrahydrofolate reductase C677T mutation. Based on these findings, it was concluded that the synergistic effects of multiple, genetic, and acquired prothrombotic risk factors brought about the hypercoagulable state that resulted in overt stroke in a thalassemic patient in early childhood.
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PMID:Arterial ischemic stroke in a child with beta-thalassemia trait and methylentetrahydrofolate reductase mutation. 1762 84


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