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Thalassaemia Intermedia (thalassaemia + intermedia)
Selected Abstracts,-Thalassaemia intermedia in a Turkish girl: homozygosity for G,A substitution at +22 relative to the ,-globin cap siteBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001R. Öner We provide the first description of a homozygote patient for the G,A substitution in the 5, UTR of the ,-globin gene. The proband was a 17-year-old girl with ,-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7·6 g/dl, Hb A2 5·4% and Hb F 14·6% of the total Hb. The Hb A2 of both parents was 3·5%. The Hb F level in the mother and father were 0·9, 1·2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the ,-gene region of the propositus revealed homozygosity for a G,A substitution at nucleotide +22 relative to the ,-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G,A mutation on the expression of ,-gene. Phenotypic expression of this homozygous patient is highly suggestive that G,A substitution at nt +22 confers a relatively mild (silent) ,+ -thalassaemia phenotype. [source] An interplay of alleviating mutations in the clinical phenotype of ,-thalassaemia intermediaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2004A. NADKARNI Summary Prediction of a , -thalassaemia major phenotype from the , -genotype is generally relatively straightforward. However, despite the ability to accurately define the , -thalassaemia mutations, prediction of a , -thalassaemia intermedia phenotype from the genotype sometimes remains problematic and this has important implications in genetic counselling and prenatal diagnosis. We report a 11-year-old Indian male child with a thalassaemia intermedia phenotype. , -Globin gene analysis of the family showed that he was a compound heterozygote with the ,88 (C,T) ,+ -mutation and the IVS1 nt 130 (G,C) ,0 -mutation. Both these mutations are rare among Indians. The propositus was also found to be heterozygous for the XmnI polymorphism and had a normal , -genotype. In this family interplay of two alleviating mutations (a milder promoter mutation along with a gene for raised HbF) might have synergistically compensated for lack of globin chains in the patient. Hence, the nature of the , -genotype as well as the knowledge of the presence or absence of alleviating factors will help the clinician to decide whether early commencement of a regular transfusion regime is necessary. [source] Treatment with deferasirox (Exjade®) effectively decreases iron burden in patients with thalassaemia intermedia: results of a pilot studyBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2010Ersi Voskaridou No abstract is available for this article. [source] Phenylhydrazine as a partial model for ,-thalassaemia red blood cell hemodynamic propertiesBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Yuval Ramot Summary ,-Thalassaemia is a congenital haemoglobinopathy, associated with red blood cells (RBC) anomalies, leading to impairment of their flow-affecting properties, namely, RBC deformability, self-aggregability, and adherence to endothelial cells (EC). Treatment of normal RBC with phenylhydrazine (PHZ) causes selective association of oxidized ,-globin chains with the membrane skeleton, leading to reduced RBC deformability, characteristic of ,-thalassaemia. PHZ has thus been used to mimic phenotypes of ,-thalassaemia RBC. The present study was undertaken to further elucidate the suitability of PHZ-treated RBC as a model for ,-thalassemic RBC, by comparing the aggregability and adhesiveness of PHZ-treated RBC to those of RBC from thalassaemia intermedia (TI) patients, using image analysis of RBC under flow. In addition, the externalization of phosphatidylserine (PS), a mediator of RBC/EC interaction, was determined. It was found that PHZ caused enhanced RBC adhesiveness to extracellular matrix, similar to TI-RBC. Furthermore, in both conditions, the enhanced adhesiveness was mediated by PS translocated to the RBC surface. In contrast, PHZ treatment completely abolished RBC aggregability, while TI-RBC aggregability was slightly elevated. It is proposed that PHZ-treated RBC resemble ,-thalassaemia RBC in their deformability and adhesiveness, but not in their aggregability, and thus can be used as a limited model for ,-thalassaemia RBC phenotypes. [source] ,-Thalassaemia intermedia in a Turkish girl: homozygosity for G,A substitution at +22 relative to the ,-globin cap siteBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2001R. Öner We provide the first description of a homozygote patient for the G,A substitution in the 5, UTR of the ,-globin gene. The proband was a 17-year-old girl with ,-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7·6 g/dl, Hb A2 5·4% and Hb F 14·6% of the total Hb. The Hb A2 of both parents was 3·5%. The Hb F level in the mother and father were 0·9, 1·2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the ,-gene region of the propositus revealed homozygosity for a G,A substitution at nucleotide +22 relative to the ,-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G,A mutation on the expression of ,-gene. Phenotypic expression of this homozygous patient is highly suggestive that G,A substitution at nt +22 confers a relatively mild (silent) ,+ -thalassaemia phenotype. [source] | ||||||||||