1/15. A rare mutation [IVS-I-130 (G-A)] in a Turkish beta-thalassemia major patient.Here we describe the identification of the rare beta-thalassemia mutation IVS-I-130 (G-A) for the first time in turkey. The hematological evaluation of the patient showed classical signs of beta-thalassemia major requiring regular blood transfusions every 30-35 days. dna analysis was carried out using reverse dot-blot hybridization and restriction endonuclease digestion, as well as genomic sequencing. The patient was found to be heterozygous for the IVS-I-6 (T-C) and IVS-I-130 (G-A) mutations. In order to deduce a possible origin for the IVS-I-130 (G-A) mutation, the sequence polymorphisms in the dna of the patient and her family were characterized. The method included the analysis of nine polymorphic nucleotides and the hypervariable microsatellite of composite sequence (AT)(x)T(y) 5' to the beta-globin gene by dna sequencing. The sequence haplotype (HT4) carrying the IVS-I-130 (G-A) mutation is also observed in algeria. This favors a Northeastern African origin for this allele. The observed results agree well with a recent introduction of this mutation to turkey from egypt toward the end of the 19th century.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/15. up-regulation of cell growth associated with an extra y chromosome in a child with beta-thalassemia major having undergone hematopoietic stem cell transplant.An extra y chromosome(s) is occasionally found in patients with various hematologic neoplasias; however, an association with hereditary blood diseases is unknown. In a child with beta-thalassemia who received a transplant with sex-mismatched umbilical cord blood and neonatal blood, fluorescent in situ hybridization (FISH) with probes to X and Y chromosomes revealed an extra Y signal in 19.3% of the hepatocytes and in 38.9% of the pretransplant peripheral blood cells, yielding YY/Y ratios of 0.24 and 0.64, respectively. In granulocyte colony-stimulating factor-mobilized autologous peripheral blood stem cells, the FISH ratio of interphase XYY cells to XY cells was 1.64, and there were 3.4 times more G-banded XYY metaphases than normal metaphases. Both FISH and polymerase chain reaction persistently demonstrated posttransplant mixed chimerism. There was a greater proportion of residual autologous XYY cells than XY cells with a mean posttransplant YY/Y ratio of 1.56 (n = 13) (1 SD = 0.33; range, 1.10 to 2.17). in vitro clonogenic assays yielded a normal number of colony-forming units but no growth in cultures without growth factor supplement. This study suggests that hematopoietic stem cells with an extra y chromosome may upregulate cell growth in response to cytokine stimulation. A posttransplant preponderance of XYY cells might be attributable to an extra y chromosome in hematopoietic stem cells withstanding the myeloablative conditioning regimen.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/15. Beta( )-thalassemia with hemochromatosis.A 64-year-old man was admitted due to ascites. Laboratory data showed hemoglobin 6.7 g/dl, mean corpuscular volume 82 fl, and ferritin 2,360 ng/ml. liver biopsy showed hemochromatosis. The diagnosis of beta-thalassemia was suggested by a decreased ratio of beta/alpha-globin synthesis in vitro (0.26). Cloning of the beta-globin gene showed A-to-G mutation in the first base of the ATA box. He was confirmed to be homozygous for this specific allele by beta-gene complex analysis and analysis of Southern blot hybridization of the alpha- and beta-globin genes. His two sons were confirmed to be heterozygous for this allele.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/15. Hb Dhonburi (Neapolis) [beta126(H4)Val-->Gly] identified in a family from northern iran.Thalassemias are the most common hereditary diseases in iran, resulting from synthesis defects in one or more hemoglobin (Hb) subunits. The majority of patients suffer from beta-thalassemia (thal), but cases with microcytic hypochromic anemia and normal electrophoretic patterns are suspected to have alpha- or silent beta-thal. A family from the northern part of iran, an area highly prevalent for thalassemias, was referred to us for prenatal diagnosis. The hematological data of the father indicated a pattern of beta-thal minor. Reverse hybridization analysis for the most common beta-globin mutations identified IVS-II-1 (G-->A) in the heterozygous state. The maternal laboratory data indicated a case more compatible with alpha-thal. iron deficient anemia was ruled out, and common alpha-thal point mutations and deletions were investigated. As no mutation was detected, chain synthesis was performed and showed an alpha/beta chain ratio of 2.1, that was in the range of beta-thal minor. dna sequencing of the entire beta-globin gene identified a heterozygous GTG-->GGG (Val-->Gly) mutation at codon 126, also known as Hb Dhonburi (Neapolis). prenatal diagnosis of the fetal dna showed the absence of the IVS-II-1 and codon 126 anomalies. This result demonstrates the importance of screening of individuals with mild microcytic hypochromic anemia for both alpha- and silent beta-thal mutations.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/15. combination of IVS2.849 A-G witH IVS1.1 G-A: a mutation of beta-globin gene in a Turkish beta-thalessemia major patient.beta-thalassemia, which is an autosomal recessive disease, is among the most common hemoglobinopathies in Antalya, turkey. Mutations found in Turkish beta-thalassemia patients constitute a heterogeneous group, which is mostly composed of point mutations and, only in very rare cases, a deletion or an insertion causes affected or carrier phenotypes. Reverse dot blot hybridization (RDBH) method is used for screening common mutations, and sequence analysis and silver staining were performed consecutively to detect any uncommon mutation. The authors report a first Turkish family with a rare variant--intervening sequence 2 (IVS2) 849 (A-G). The proband's mother and father were determined as carriers of IVS2.849 (A-G) and IVS1.1 (G-A) mutations, respectively. Proband is the first child of the family and she has an IVS2.849 (A-G)/IVS1.1 (G-A) genotype with ss-thalassemia major phenotype. prenatal diagnosis was performed for the second child, and genotype of the fetus was determined as IVS2.849 (A-G)/Normal. This first report of IVS2.849 (A-G) mutation in Turkish population shows that there are many more mutations contributing the heterogeneity of the mutation spectrum of beta-globin gene in the Turkish population, which indicates migrations of different ethnic origins.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/15. Two rare mutations in turkey: IVS I.130(G-C) and IVS II.848(C-A).beta-thalassemia, an autosomal recessive disease, results from mutations of the beta-globin gene. More than 40 different mutations found in Turkish beta-thalassemia patients are mostly composed of point mutations, and only in very rare cases a deletion or an insertion causes beta-thalassemia phenotypes. Here, we report two patients who were clinically diagnosed with beta-thalassemia major and HbS/beta-thalassemia respectively. We performed reverse dot blot hybridization method and automated sequence analysis to detect the mutations. One of the patients was found to be IVS I.130 (G-C) homozygous, the other was HbS/IVS II.848 (C-A) as compound heterozygous. The aim of this study was to report hematological and clinical findings in both cases related with beta-globin gene defects that are very rare.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/15. A novel Mediterranean "delta beta-thalassemia" determinant containing the delta ( ) 27 and beta (0) 39 point mutations in cis.The term delta beta-thalassemia with normal HbF has been recently proposed to define heterogenous delta and beta globin gene molecular defects involving the same chromosome in cis. Here, we describe a Sardinian family in which three members showing microcytosis, border-line HbA2 levels and normal HbF proved to be heterozygotes for delta( ) 27 and beta(0) 39 point mutations in cis by allele specific oligonucleotide hybridization as well as by ECO 0 109 I endonuclease digestion and electrophoresis. As some of these beta-thalassemia carriers shows normal HbA2 levels, knowledge of the molecular basis of this novel delta beta-thalassemia silent phenotype would be useful in thalassemia screening and genetic counselling.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/15. Hb Lulu Island (alpha 2 beta 2 107[G9]Gly-->Asp)-beta zero- thalassemia (codon 15; TGG-->TAG), a form of thalassemia intermedia.Hb Lulu Island [beta 107(G9)Gly-->Asp] was discovered in an East Indian female who carried a common beta zero-thalassemia allele, i.e., codon 15, TGG-->TAG (is a stop codon) in trans. Both abnormalities were detected through sequencing of the amplified beta-globin genes and were confirmed by hybridization with 32P-labeled probes. Hb Lulu Island is mildly unstable with a borderline decrease in oxygen affinity; its instability is less severe than that of Hb Burke or beta 107(G9)Gly-->Arg. The compound heterozygosity expresses as a thalassemia intermedia with moderate anemia, a variable need for blood transfusions, Heinz body formation, and a red cell morphology which is typical for such a condition. The level of HbA2 was greatly increased (6.5-7.0%) as was the delta chain level (12% of total non-alpha) probably because of the instability of Hb Lulu Island and the decreased ability of the beta x chain to form dimers with the normal alpha chain.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/15. Hb Hradec Kralove (Hb HK) or alpha 2 beta 2 115(G17)Ala-->Asp, a severely unstable hemoglobin variant resulting in a dominant beta-thalassemia trait in a Czech family.We have identified through sequencing of amplified dna a GCC-->GAC mutation in codon 115 of the beta-globin gene in a mother and daughter of a small Czech family. This base change was confirmed by hybridization with a 32P-labeled specific oligonucleotide probe and by gene mapping because it creates a new Ava II site. The mutation results in an Ala-->Asp replacement at beta 115(G17); this beta chain is severely unstable and could not be identified either as chain or as hemoglobin variant by isoelectrofocusing and various high performance liquid chromatography methods. Stability tests were mildly positive in freshly prepared lysates, but an unstable hemoglobin could not be detected in older lysates with these methods. Its presence results in a dominant type of beta-thalassemia in the two heterozygotes, with moderate anemia, reticulocytosis, nucleated red cells, target cells, and other red cell changes, Heinz body formation, and splenomegaly; the oldest of the two patients was splenectomized. Both subjects had a marked increase in fetal hemoglobin synthesis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/15. A novel beta-thalassaemia mutation in the 5' untranslated region of the beta-globin gene.A thymidine deletion at position 10 of the 5' untranslated region of the beta-globin gene was detected in a beta-thalassaemia intermedia patient carrying a beta(0)39 stop codon mutation on the other chromosome; this new mutation, 10(-T), was detected by automated fluorescent dna sequencing and verified by dot-blot allele-specific hybridizations. The 10(-T) mutation is a 'silent carrier', is associated with a reduced amount of steady-state beta-globin mRNA, and establishes a connection between the 5' untranslated region of the beta-globin gene and the regulation of its expression.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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