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Hereditary Persistence (hereditary + persistence)

Distribution by Scientific Domains
Medical Sciences85%

Selected Abstracts

An optimized method to separate reticulocytes from peripheral blood for molecular analysis

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2009
R. PETRUZZELLI
Summary A method based on immunomagnetic sorting of reticulocytes from peripheral blood was set up and combined to a commercial extraction kit for the isolation of total RNA from whole blood. This procedure resulted in high-quality RNA samples suitable for molecular analysis. We used this procedure to analyse erythroid-specific transcripts, starting from peripheral blood samples, to search for differently expressed mRNAs in patients with hereditary persistence of foetal haemoglobin. After erythrocyte lysis, CD15+and CD45+ peripheral cells were negatively sorted to remove leucocyte populations that could have affected the subsequent screening procedure. The cell sorting and RNA extraction procedure was completed within 1,2 h of erythrocyte lysis, which represents a consistent saving of time compared with other procedures. Moreover, it produced 1 ,g of total RNA per ml of blood samples, which is sufficient for molecular analysis. Therefore, our method is a reliable and efficient tool to isolate RNA from specific cell subpopulations poorly represented in peripheral blood, particularly when accurate detection and characterization of highly unstable and poorly expressed molecules is required. [source]

Evaluation of F cells in sickle cell disorders by flow cytometry , comparison with the Kleihauer,Betke's slide method

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2007
K. Y. ITALIA
Summary Adult F cell numbers are raised in inherited haemoglobin disorders, such as , -thalassaemia and sickle cell anaemia, hereditary persistence of foetal haemoglobin, and some acquired conditions, such as juvenile myelomonocytic leukaemia, during acute erythropoietic stress and pregnancy. True foetal erythrocytes containing foetal amounts of HbF can also occur in the adult circulation during the leakage of HbF-containing cells from the foetus to the maternal circulation. In normal adults, HbF is restricted to a small proportion (3,7%) of red blood cells (RBC), termed ,F cells'. Techniques estimating the amount of HbF use lysates prepared from RBC, whereas those that estimate the adult F cell count use intact RBC. An accurate assessment of adult F cells in sickle cell disorders is important because increased adult F cells are associated with decreased morbidity in these disorders. In the present study, HbF levels were measured and adult F cell numbers were estimated in 100 blood samples (25 normal individuals, 25 sickle heterozygotes, 25 sickle homozygotes and 25 sickle , -thalassaemia cases), using high pressure liquid chromatography for HbF levels, and flow cytometry and the Kleihauer,Betke (KB) acid elution microscope slide method for cell counts. Flow cytometry gave a more accurate assessment of adult F cells, eliminating any manual error, as compared to KB, which was less sensitive and precise as it is based on subjective visual interpretation. [source]

Disorders of the synthesis of human fetal hemoglobin

IUBMB LIFE, Issue 2 2008
Laura Manca
Abstract Fetal hemoglobin (HbF), the predominant hemoglobin in the fetus, is a mixture of two molecular species (,2G,2 and ,2A,2) that differ only at position 136 reflecting the products of two nonallelic ,-globin genes. At the time of birth, HbF accounts for ,70% of the total Hb. The G,:A, globin ratio in the HbF of normal newborn is 70:30 whereas in the trace amounts of HbF that is found in the adult it reverses to 40:60 because of a ,- to ,-globin gene switch. Alterations of these ratios are indicative of a molecular defect at the level of the HbF synthesis. Qualitative hemoglobinopathies due to G, and A, chain structural variants, and quantitative hemoglobinopathies affecting the synthesis of HbF such as ,-thalassemias, duplications, triplications, and even sextuplications of the ,-globin genes, which may be detected in newborn blood lysates, have been described. Moreover, several pathological and nonpathological conditions affecting the ,-globin gene cluster, such as ,-thalassemia, sickle cell disease, ,,-thalassemia, and hereditary persistence of HbF syndromes, are characterized by the continued synthesis of ,-globin chains in the adult life. Studies of these natural mutants associated with increased synthesis of HbF in adult life have provided considerable insight into the understanding of the control of globin gene expression and Hb switching. © 2008 IUBMB IUBMB Life, 60(2): 94,111, 2008 [source]

Hemoglobin Kenya composed of ,- and (A,,)-fusion-globin chains, associated with hereditary persistence of fetal hemoglobin

AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2009
Ibifiri Wilcox
Hb Kenya is made up of two normal ,-globin chains and two A,,-fusion globin chains. The latter are the product of an A,,-hybrid globin gene formed as a result of misalignment during meiosis and nonhomologous crossing over. It is associated with a deletion of 22.7 kb including the ,-globin gene, between the A,- and ,-globin genes. Hb Kenya is found in Kenyans and Ugandans. Heterozygotes have moderately increased Hb F, and this mutation has been known as an (A,,)+ hereditary persistence of fetal hemoglobin (HPFH). Compound heterozygotes for Hb Kenya/Hb S are thought to be asymptomatic, but reports of long term follow-up of these patients are lacking. The correct identification of Hb Kenya is sometimes problematic. In cation exchange high performance liquid chromatography, Hb Kenya elutes in similar position as Hb A2, Hb Lepore, Hb E, and several other variant hemoglobins. Definitive diagnosis that is necessary for proper patient management is best done by DNA-based gap-PCR tests. Am. J. Hematol, 2009. © 2008 Wiley-Liss, Inc. [source]

Compound heterozygosity of non-deletional hereditary persistence of fetal hemoglobin and ,,-thalassemia,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008
Angelos Kalamaras
No abstract is available for this article. [source]

research paper: Role of the cold shock domain protein A in the transcriptional regulation of HBG expression

BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2010
Raffaella Petruzzelli
Summary Impaired switching from fetal haemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal haemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate ,-thalassaemia and sickle cell anaemia. Fetal haemoglobin levels are regulated by complex mechanisms involving factors linked or not to the ,-globin gene (HBB) locus. To search for factors putatively involved in the expression of the ,-globin genes (HBG1, HBG2), we examined the reticulocyte transcriptome of three siblings who had different HbF levels and different degrees of ,-thalassaemia severity although they had the same ,BA - and ,,B cluster genotypes. By mRNA differential display we isolated the cDNA coding for the cold shock domain protein A (CSDA), also known as dbpA, previously reported to interact in vitro with the HBG2 promoter. Expression studies performed in K562 and in primary erythroid cells showed an inverse relationship between HBG and CSDA expression levels. Functional studies performed by Chromatin Immunoprecipitation and reporter gene assays in K562 cells demonstrated that CSDA is able to bind the HBG2 promoter and suppress its expression. Therefore, our study demonstrated that CSDA is a trans-acting repressor factor of HBG expression and modulates the HPFH phenotype. [source]