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Piero C Giordano - One of the best experts on this subject based on the ideXlab platform.
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segmental duplications involving the α globin gene cluster are causing β thalassemia intermedia phenotypes in β thalassemia heterozygous patients
Blood Cells Molecules and Diseases, 2008Co-Authors: Cornelis L Harteveld, Maria Domenica Cappellini, Chiara Refaldi, Elena Cassinerio, Piero C GiordanoAbstract:Abstract We describe two cases of simple heterozygosity for the common β°-thalassemia mutation β39 (C → T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or Red Cell Enzyme deficiencies were excluded. In one case a triplication of the α-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the α-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the α-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-α3.7 triplication in trans, resulting in a total of 7 active α-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active α-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of α-globin genes duplication defects in cases of β-thalassemia heterozygotes with thalassemia intermedia phenotypes.
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segmental duplications involving the alpha globin gene cluster are causing beta thalassemia intermedia phenotypes in beta thalassemia heterozygous patients
Blood Cells Molecules and Diseases, 2008Co-Authors: Cornelis L Harteveld, Maria Domenica Cappellini, Chiara Refaldi, Elena Cassinerio, Piero C GiordanoAbstract:We describe two cases of simple heterozygosity for the common beta degrees -thalassemia mutation beta 39 (C-->T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or Red Cell Enzyme deficiencies were excluded. In one case a triplication of the alpha-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the alpha-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the alpha-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-alpha(3.7) triplication in trans, resulting in a total of 7 active alpha-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active alpha-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of alpha-globin genes duplication defects in cases of beta-thalassemia heterozygotes with thalassemia intermedia phenotypes.
Giovanna Valentini - One of the best experts on this subject based on the ideXlab platform.
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pyruvate kinase deficiency the genotype phenotype association
Blood Reviews, 2007Co-Authors: Alberto Zanella, Paola Bianchi, Elisa Fermo, Laurent R Chiarelli, Giovanna ValentiniAbstract:Red Cell pyruvate kinase (PK) deficiency is the most frequent Enzyme abnormality of glycolysis causing chronic non-spherocytic haemolytic anaemia. The disease is transmitted as an autosomal recessive trait, clinical symptoms usually occurring in compound heterozygotes for two mutant alleles and in homozygotes. The severity of haemolysis is highly variable, ranging from very mild or fully compensated forms to life-threatening neonatal anaemia necessitating exchange transfusions. Erythrocyte PK is synthesised under the control of the PK-LR gene located on chromosome 1. One hundRed eighty different mutations in PK-LR gene, mostly missense, have been so far reported associated to PK deficiency. First attempts to delineate the genotype-phenotype association were mainly based on the analysis of the Enzyme's three-dimensional structure and the observation of the few homozygous patients. More recently, the comparison of the recombinant mutants of human Red Cell PK with the wild-type Enzyme has enabled the effects of amino acid replacements on the Enzyme molecular properties to be determined. However, the clinical manifestations of Red Cell Enzyme defects are not merely dependent on the molecular properties of the mutant protein but rather reflect the complex interactions of additional factors, including genetic background, concomitant functional polymorphisms of other Enzymes, posttranslational or epigenetic modifications, ineffective erythropoiesis and differences in splenic function.
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two new mutations of the p5 n 1 gene found in italian patients with heReditary hemolytic anemia the molecular basis of the Red Cell Enzyme disorder
Haematologica, 2006Co-Authors: Laurent R Chiarelli, Alberto Zanella, Paola Bianchi, Elisa Fermo, Patrizia Abrusci, Chiara Dellacasa, Alessandro Galizzi, Giovanna ValentiniAbstract:Inherited pyrimidine 5'-nucleotidase type-1 (P5'N-1) deficiency is the most frequent abnormality of Red Cell nucleotide metabolism causing non-spherocytic hemolytic anemia. We describe two novel mutations in two Italian patients affected by P5'N-1 deficiency. One mutation is a two base deletion that occurs at the splice site junction between intron 7 and exon 8 (c.396-397del AG); the second is an in-frame deletion of three adjacent bases (c.427-429del CAA), leading to deletion of glutamine 143. The kinetic properties of Q143del variant were not grossly alteRed, but the variant was very heat unstable even at physiological temperatures.
Cornelis L Harteveld - One of the best experts on this subject based on the ideXlab platform.
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segmental duplications involving the α globin gene cluster are causing β thalassemia intermedia phenotypes in β thalassemia heterozygous patients
Blood Cells Molecules and Diseases, 2008Co-Authors: Cornelis L Harteveld, Maria Domenica Cappellini, Chiara Refaldi, Elena Cassinerio, Piero C GiordanoAbstract:Abstract We describe two cases of simple heterozygosity for the common β°-thalassemia mutation β39 (C → T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or Red Cell Enzyme deficiencies were excluded. In one case a triplication of the α-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the α-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the α-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-α3.7 triplication in trans, resulting in a total of 7 active α-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active α-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of α-globin genes duplication defects in cases of β-thalassemia heterozygotes with thalassemia intermedia phenotypes.
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segmental duplications involving the alpha globin gene cluster are causing beta thalassemia intermedia phenotypes in beta thalassemia heterozygous patients
Blood Cells Molecules and Diseases, 2008Co-Authors: Cornelis L Harteveld, Maria Domenica Cappellini, Chiara Refaldi, Elena Cassinerio, Piero C GiordanoAbstract:We describe two cases of simple heterozygosity for the common beta degrees -thalassemia mutation beta 39 (C-->T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or Red Cell Enzyme deficiencies were excluded. In one case a triplication of the alpha-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the alpha-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the alpha-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-alpha(3.7) triplication in trans, resulting in a total of 7 active alpha-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active alpha-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of alpha-globin genes duplication defects in cases of beta-thalassemia heterozygotes with thalassemia intermedia phenotypes.
T. Varga - One of the best experts on this subject based on the ideXlab platform.
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Original Communication - Red Cell Enzyme and serum protein polymorphisms (ACP1, PGM1, GLO1, ESD, HP, PI) in Turkish population
Medknow Publications on behalf of Indian Society of Human Genetics, 2005Co-Authors: L. Dönbak, C. Csete, S. Salaçin, T. VargaAbstract:Background: The allele frequencies in human populations are used in different areas such as population genetics, forensic genetics and anthropological studies. Various different populations have been investigated their allele frequency distributions of polymorphic traits. Aims and Objectives: The allele frequency distributions of four Red Cell Enzyme (ACP1, PGM1, GLO1, ESD) and two serum protein systems (HP, PI subtypes) were analyzed in Turkish population from Adana area, Turkey, in order to enlarge our knowledge on the genetic composition of Turkish population. Material and Methods: Venous blood samples taken from 200 unrelated Turkish individuals were transported to the Forensic Serology Laboratory of Albert Szent-Gy φrgyi Medical University (Szeged/Hungary) for phenotyping. The phenotypes of ACP1, PGM1, GLO1, ESD, and HP systems were determined by means of starch gel electrophoresis, while PI subtypes were obtained by polyacrylamide gel isoelectric focusing method. The allele frequencies were calculated by gene counting. Results: The calculated frequencies of the alleles are as follows: ACP1*A = 0.250 ± 0.021, ACP1*B = 0.693 ± 0.023, ACP1*C = 0.057 ± 0.011; PGM1*1 = 0.710 ± 0.022, PGM1*2 = 0.288 ± 0.022, PGM1*6 = 0.002 ± 0.002; GLO1*1 = 0.373 ± 0.024, GLO1*2 = 0.627 ± 0.024; ESD*1 = 0.805 ± 0.019, ESD*2 = 0.195 ± 0.019; HP*1 = 0.265 ± 0.022, HP*2 = 0.735 ± 0.022; PI*M1 = 0.887 ± 0.015, PI*M2 = 0.010 ± 0.004, PI*M3 = 0.095 ± 0.014, PI*S = 0.008 ± 0.004. Conclusions: The comparison of the data with those of Asian and European populations showed that the allele frequencies of ACP1, ESD and HP are similar or close to those of Asian populations, whereas those of PGM1 and PI come close to European populations. The allele frequency of GLO1 system is inbetween those of Asians and European
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Red Cell Enzyme and serum protein polymorphisms (ACP1, PGM1, GLO1, ESD, HP, PI) in Turkish population
Indian Journal of Human Genetics, 2005Co-Authors: L. Dönbak, C. Csete, S. Salaçin, T. VargaAbstract:BACKGROUND: The allele frequencies in human populations are used in different areas such as population genetics, forensic genetics and anthropological studies. Various different populations have been investigated their allele frequency distributions of polymorphic traits. AIMS AND OBJECTIVES: The allele frequency distributions of four Red Cell Enzyme (ACP1, PGM1, GLO1, ESD) and two serum protein systems (HP, PI subtypes) were analyzed in Turkish population from Adana area, Turkey, in order to enlarge our knowledge on the genetic composition of Turkish population. MATERIAL AND METHODS: Venous blood samples taken from 200 unrelated Turkish individuals were transported to the Forensic Serology Laboratory of Albert Szent-Gyorgyi Medical University (Szeged/Hungary) for phenotyping. The phenotypes of ACP1, PGM1, GLO1, ESD, and HP systems were determined by means of starch gel electrophoresis, while PI subtypes were obtained by polyacrylamide gel isoelectric focusing method. The allele frequencies were calculated by gene counting. RESULTS: The calculated frequencies of the alleles are as follows: ACP1*A = 0.250 ± 0.021, ACP1 *B = 0.693 ± 0.023, ACP1 *C = 0.057 ± 0.011; PGM1 *1 = 0.710 ± 0.022, PGM1*2 = 0.288 ± 0.022, PGM1*6 = 0.002 ± 0.002; GLO1*1 = 0.373 ± 0.024, GLO1*2 = 0.627 ± 0.024; ESD*1 = 0.805 ± 0.019, ESD*2 = 0.195 ± 0.019; HP*1 = 0.265 ± 0.022, HP*2 = 0.735 ± 0.022; PI*M1 = 0.887 ± 0.015, PI*M2 = 0.010 ± 0.004, PI*M3 = 0.095 ± 0.014, PI*S = 0.008 ± 0.004. CONCLUSIONS: The comparison of the data with those of Asian and European populations showed that the allele frequencies of ACP1, ESD and HP are similar or close to those of Asian populations, whereas those of PGM1 and PI come close to European populations. The allele frequency of GLO1 system is inbetween those of Asians and Europeans.
Maria Domenica Cappellini - One of the best experts on this subject based on the ideXlab platform.
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segmental duplications involving the α globin gene cluster are causing β thalassemia intermedia phenotypes in β thalassemia heterozygous patients
Blood Cells Molecules and Diseases, 2008Co-Authors: Cornelis L Harteveld, Maria Domenica Cappellini, Chiara Refaldi, Elena Cassinerio, Piero C GiordanoAbstract:Abstract We describe two cases of simple heterozygosity for the common β°-thalassemia mutation β39 (C → T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or Red Cell Enzyme deficiencies were excluded. In one case a triplication of the α-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the α-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the α-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-α3.7 triplication in trans, resulting in a total of 7 active α-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active α-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of α-globin genes duplication defects in cases of β-thalassemia heterozygotes with thalassemia intermedia phenotypes.
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segmental duplications involving the alpha globin gene cluster are causing beta thalassemia intermedia phenotypes in beta thalassemia heterozygous patients
Blood Cells Molecules and Diseases, 2008Co-Authors: Cornelis L Harteveld, Maria Domenica Cappellini, Chiara Refaldi, Elena Cassinerio, Piero C GiordanoAbstract:We describe two cases of simple heterozygosity for the common beta degrees -thalassemia mutation beta 39 (C-->T), both presenting with a thalassemia intermedia phenotype. In both cases synergic effect deriving from membrane defects or Red Cell Enzyme deficiencies were excluded. In one case a triplication of the alpha-globin genes was found which did not justify the severity of the transfusion-dependent phenotype. Multiplex ligation-dependent probe amplification (MLPA) analysis of the alpha-globin gene cluster revealed two new rearrangements, consisting of a full duplication of the alpha-globin genes locus including the upstream regulatory element. In one case the duplication was in the presence of the common anti-alpha(3.7) triplication in trans, resulting in a total of 7 active alpha-globin genes. In the other case the duplicated allele and the normal allele in trans resulted into a total of 6 active alpha-globin genes. We report the clinical and hematological data and the molecular analysis and discuss the occurrence of alpha-globin genes duplication defects in cases of beta-thalassemia heterozygotes with thalassemia intermedia phenotypes.