scholarly journals Hemoglobin Cagliari (beta 60 [E4] Val----Glu): a novel unstable thalassemic hemoglobinopathy

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 371-375 ◽  
Author(s):  
A Podda ◽  
R Galanello ◽  
L Maccioni ◽  
MA Melis ◽  
C Rosatelli ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Peripheral Blood ◽  
De Novo ◽  
Globin Gene ◽  
De Novo Mutation ◽  
Beta Globin ◽  
Globin Chain ◽  
Thalassemia Intermedia ◽  
Protein Structural Analysis ◽  
Chain Synthesis

Abstract This report describes a patient with thalassemia intermedia-like phenotype born to normal parents in whom globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T to A substitution at codon 60 of the beta-globin gene arising as a de novo mutation. Normal sequences were detected at the homologous beta-globin locus. This mutation results in the substitution of a polar (glutamic acid) for a nonpolar (valine) residue near the corner of the heme pocket of the beta-globin chain. The novel variant has been designated Hb Cagliari, from the place of birth of the propositus. Kinetics of globin synthesis performed following splenectomy suggest that this new Hb variant is synthesized at a near normal rate but undergoes rapid breakdown. The extreme lability of the variant explains the clinical and hematologic picture characterized by marked ineffective erythropoiesis, thalassemia-like bone changes, iron overload, high proportion of Hb F in the peripheral blood, reduced beta/alpha-globin chain synthesis ratio in peripheral blood reticulocytes, and absence of the abnormal Hb in peripheral blood at extensive protein structural analysis before splenectomy. This case indicates that a thalassemic hemoglobinopathy should be suspected in the presence of a patient with a thalassemia intermedia-like phenotype born to normal parents, even when protein structural analysis fails to detect an abnormal Hb. DNA sequencing may allow to define the mutation, thus making the proper diagnosis.

scholarly journals Hemoglobin Cagliari (beta 60 [E4] Val----Glu): a novel unstable thalassemic hemoglobinopathy

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 371-375
Author(s):  
A Podda ◽  
R Galanello ◽  
L Maccioni ◽  
MA Melis ◽  
C Rosatelli ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Peripheral Blood ◽  
De Novo ◽  
Globin Gene ◽  
De Novo Mutation ◽  
Beta Globin ◽  
Globin Chain ◽  
Thalassemia Intermedia ◽  
Protein Structural Analysis ◽  
Chain Synthesis

This report describes a patient with thalassemia intermedia-like phenotype born to normal parents in whom globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T to A substitution at codon 60 of the beta-globin gene arising as a de novo mutation. Normal sequences were detected at the homologous beta-globin locus. This mutation results in the substitution of a polar (glutamic acid) for a nonpolar (valine) residue near the corner of the heme pocket of the beta-globin chain. The novel variant has been designated Hb Cagliari, from the place of birth of the propositus. Kinetics of globin synthesis performed following splenectomy suggest that this new Hb variant is synthesized at a near normal rate but undergoes rapid breakdown. The extreme lability of the variant explains the clinical and hematologic picture characterized by marked ineffective erythropoiesis, thalassemia-like bone changes, iron overload, high proportion of Hb F in the peripheral blood, reduced beta/alpha-globin chain synthesis ratio in peripheral blood reticulocytes, and absence of the abnormal Hb in peripheral blood at extensive protein structural analysis before splenectomy. This case indicates that a thalassemic hemoglobinopathy should be suspected in the presence of a patient with a thalassemia intermedia-like phenotype born to normal parents, even when protein structural analysis fails to detect an abnormal Hb. DNA sequencing may allow to define the mutation, thus making the proper diagnosis.

scholarly journals Rare double heterozygosity for poly A(A>G) and CD17(A>T) of beta thalassemia intermedia in a Chinese family

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Jianhong Xie ◽  
Yuqiu Zhou ◽  
Qizhi Xiao ◽  
Ruoting Long ◽  
Lianxiang Li ◽  
...  
Keyword(s):  
Globin Gene ◽  
Carrier State ◽  
Beta Thalassemia ◽  
Chinese Family ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Wide Range ◽  
Chain Synthesis ◽  
Double Heterozygosity ◽  
Globin Chain Synthesis

Beta thalassemia is a hereditary disorder resulted from mutations in the β globin gene leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. Three types have been defined, based on the degree of reduced beta-globin chain synthesis and clinical phenotype: major, intermedia and minor (heterozygote carrier state). Beta thalassemia intermedia is characterized by heterogeneity for the wide clinical spectrum of various genotypes and a wide range of presentations. The genotypes of beta thalassemia intermedia are much complicated referring to β+/β+,β+/β0, Hb E/β0, β0/β0 compounding alpha thalassemia and so on. In this present case, we reported a rare beta thalassemia intermedia genotype of double heterozygosity for poly A (A>G) and CD17(A>T) indicated of β+/β0 in a Chinese family.

scholarly journals beta-thalassemia intermedia in a Brazilian patient with - 101(C > T) and codon 39 (C > T) mutations

2003 ◽  
Vol 121 (1) ◽  
pp. 28-30
Author(s):  
Sylvia Morais de Sousa ◽  
Letícia Khater ◽  
Luís Antônio Peroni ◽  
Karine Miranda ◽  
Marcelo Jun Murai ◽  
...  
Keyword(s):  
Clinical Course ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Hypochromic Anemia ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Thalassemia Intermedia ◽  
Mean Cell Volume ◽  
Molecular Alterations ◽  
Brazilian Patient

CONTEXT: We verified molecular alterations in a 72-year-old Brazilian male patient with a clinical course of homozygous beta-thalassemia intermedia, who had undergone splenectomy and was surviving without regular blood transfusions. The blood cell count revealed microcytic and hypochromic anemia (hemoglobin = 6.5 g/dl, mean cell volume = 74 fl, mean cell hemoglobin = 24 pg) and hemoglobin electrophoresis showed fetal hemoglobin = 1.3%, hemoglobin A2 = 6.78% and hemoglobin A = 79.4%. OBJECTIVE: To identify mutations in a patient with the symptoms of beta-thalassemia intermedia. DESIGN: Molecular inquiry into the mutations possibly responsible for the clinical picture described. SETTING: The structural molecular biology and genetic engineering center of the Universidade Estadual de Campinas, Campinas, Brazil. PROCEDURES: DNA extraction was performed on the patient's blood samples. The polymerase chain reaction (PCR) was done using five specific primers that amplified exons and the promoter region of the beta globin gene. The samples were sequenced and then analyzed via computer programs. RESULTS: Two mutations that cause the disease were found: -101 (C > T) and codon 39 (C > T). CONCLUSIONS: This case represents the first description of 101 (C > T) mutation in a Brazilian population and it is associated with a benign clinical course.

scholarly journals Globin Chain Synthesis in the Marrow and Reticulocytes of Beta Thalassemia, Hemoglobin H Disease, and Beta Delta Thalassemia

Blood ◽  
1972 ◽  
Vol 40 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Mordechai Shchory ◽  
Bracha Ramot
Keyword(s):  
Bone Marrow ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Thalassemia Intermedia ◽  
Thalassemia Minor ◽  
Order Of Magnitude ◽  
Hb H Disease ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract α, β, and γ globin chain synthesis in bone marrow and peripheral blood reticulocytes were studied in two patients with thalassemia major, two with thalassemia intermedia, one with thalassemia minor, one with Hb H disease, and one with homozygous βδ-thalassemia. Nine nonthalassemic patients served as controls. In thalassemia major, a marked imbalance of α- to β-chain synthesis was found in the bone marrow as well as in reticulocytes. The imbalance, however, was slightly more evident in the latter. In the patients with thalassemia intermedia and minor the α- to β-globin chain ratios in the reticulocytes were of the same order of magnitude, despite the marked clinical differences between thalassemia intermedia and minor. A balanced synthesis was found in the bone marrow of the patient with thalassemia minor. The bone marrow globin synthesis in thalassemia intermedia was not studied. Contrary to that in Hb H disease and βδ-thalassemia, the imbalance was more apparent in the bone marrow. In the latter, no evidence for imbalance was detected in the reticulocytes. These results point out the need for further studies on globin chain synthesis in the bone marrow and reticulocytes of patients With the various thalassemia syndromes and the effect of the free globin chain pool on those results.

scholarly journals Delta +-thalassemia in Sardinia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 341-345 ◽  
Author(s):  
M Pirastu ◽  
R Galanello ◽  
MA Melis ◽  
C Brancati ◽  
A Tagarelli ◽  
...  
Keyword(s):  
Restriction Endonuclease ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Globin Chain ◽  
New Type ◽  
Polymorphic Restriction ◽  
Chain Synthesis ◽  
Double Heterozygosity ◽  
Globin Chain Synthesis

Abstract We have defined a new type of delta-thalassemia in which beta-globin chain synthesis is incompletely suppressed. Homozygotes have unusually low HbA2 levels, and double heterozygosity for this delta-thalassemia gene and beta-thalassemia normalizes the HbA2 level. The delta- thalassemia occurs on a chromosome that is identifiable using polymorphic restriction endonuclease sites. We call this condition delta +-thalassemia, to distinguish it from the previously described delta 0-thalassemia syndromes in which no delta-globin chain synthesis occurs.

scholarly journals A family with segregating triplicated alpha globin loci and beta thalassemia

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1035-1040 ◽  
Author(s):  
R Galanello ◽  
R Ruggeri ◽  
E Paglietti ◽  
M Addis ◽  
MA Melis ◽  
...  
Keyword(s):  
Globin Gene ◽  
Phenotypic Expression ◽  
Beta Thalassemia ◽  
Heterozygous State ◽  
Globin Chain ◽  
Homozygous State ◽  
Alpha Globin ◽  
Triple Alpha ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract In this article we report a Sardinian family, in which a beta- thalassemia gene and a triple alpha-globin loci, counterpart of the rightward deletion type alpha-thalassemia-2, were segregating. The analysis of the genotype-phenotype correlations in the different family members allowed us to give an outline of the manifestations associated with different genotype combinations. The heterozygote for the triple alpha-loci showed no consistent abnormal clinical or hematologic characteristics and presented balanced alpha/beta-globin chain synthesis. In the homozygous state for this lesion, the only phenotypic expression was a slightly imbalanced globin chain synthesis. The combination of heterozygous beta-thalassemia with the heterozygous state for the triple alpha-globin loci produced no clinical manifestations and showed a hematologic phenotype indistinguishable from that of heterozygous beta-thalassemia. On the other hand, the combination of the homozygous state for the triple alpha-globin gene loci and the heterozygous state for beta-thalassemia produced a clinical picture of thalassemia intermedia with a very mild clinical course, minor increase of fetal hemoglobin (HbF) levels, and a pronounced imbalance of globin chain synthesis.

scholarly journals Hypomethylation of DNA derived from purified human erythroid cells correlates with gene activity of the beta-globin cluster

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1202-1207 ◽  
Author(s):  
A Oppenheim ◽  
Y Katzir ◽  
E Fibach ◽  
A Goldfarb ◽  
E Rachmilewitz
Keyword(s):  
Peripheral Blood ◽  
Globin Gene ◽  
Genetic Regulation ◽  
Inverse Correlation ◽  
Thalassemia Major ◽  
Gene Activity ◽  
Beta Thalassemia ◽  
Globin Genes ◽  
Beta Globin ◽  
A Site

Abstract Analysis of methylation at the beta-globin gene cluster was carried out on DNA derived from nucleated RBCs (orthochromatic normoblasts) isolated from peripheral blood of patients with beta-thalassemia major or other congenital hemolytic anemia after splenectomy. A procedure to separate these normoblasts from the other nucleated cells of the peripheral blood was developed, providing us with a convenient source of DNA for investigating parameters related to human erythroid differentiation. Blood samples were obtained from six adult patients who express their gamma-globin genes at different levels. Inverse correlation between methylation and gene activity was consistently observed for five of the eight sites analyzed. A site 3′ to the beta gene was always unmethylated, two sites flanking the epsilon gene were always found to be methylated, and two sites 5′ to the two gamma genes, G gamma and A gamma, were hypomethylated in correlation with gamma gene activity of the individual patients. A site 5′ to the delta gene was unmethylated in normoblasts as well as in WBC. No apparent relation between hypomethylation and gene activity was observed for two additional sites. The results suggest that methylation at specific chromosomal locations participate in genetic regulation of the beta- like globin genes in humans.

scholarly journals Globin chain synthesis in HbD (Punjab)-beta-thalassemia

Blood ◽  
1976 ◽  
Vol 47 (1) ◽  
pp. 113-120 ◽  
Author(s):  
RF Rieder
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Globin Chains ◽  
Mild Anemia ◽  
Thalassemia Trait ◽  
Chain Synthesis ◽  
Hbd Punjab ◽  
Globin Chain Synthesis

Abstract A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta- thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.

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