The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Renzo Galanello - One of the best experts on this subject based on the ideXlab platform.
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Alpha-Thalassemia
Genetics in Medicine, 2011Co-Authors: Renzo GalanelloAbstract:Alpha-Thalassemia is one of the most common hemoglobin genetic abnormalities and is caused by the reduced or absent production of the alpha globin chains. Alpha-Thalassemia is prevalent in tropical and subtropical world regions where malaria was and still is epidemic, but as a consequence of the recent massive population migrations, Alpha-Thalassemia has become a relatively common clinical problem in North America, North Europe, and Australia. Alpha-Thalassemia is very heterogeneous at a clinical and molecular level. Four clinical conditions of increased severity are recognized: the silent carrier state, the Alpha-Thalassemia trait, the intermediate form of hemoglobin H disease, and the hemoglobin Bart hydrops fetalis syndrome that is lethal in utero or soon after birth. Alpha-Thalassemia is caused most frequently by deletions involving one or both alpha globin genes and less commonly by nondeletional defects. A large number of Alpha-Thalassemia alleles have been described and their interaction results in the wide spectrum of hematological and clinical phenotypes. Genotype-phenotype correlation has been only partly clarified. Carriers of Alpha-Thalassemia do not need any treatment. Usually, patients with hemoglobin H disease are clinically well and survive without any treatment, but occasional red blood cell transfusions may be needed if the hemoglobin level suddenly drops because of hemolytic or aplastic crisis likely due to viral infections. Hemoglobin Bart hydrops fetalis syndrome currently has no effective treatment although attempts at intrauterine transfusion and hematopoietic stem cell transplantation have been made.
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Beta-thalassemia
Genetics in Medicine, 2010Co-Authors: Renzo GalanelloAbstract:Beta-thalassemia is caused by the reduced (beta^+) or absent (beta^0) synthesis of the beta globin chains of the hemoglobin tetramer. Three clinical and hematological conditions of increasing severity are recognized, i.e., the beta-thalassemia carrier state, thalassemia intermedia, and thalassemia major. The beta-thalassemia carrier state, which results from heterozygosity for beta-thalassemia, is clinically asymptomatic and is defined by specific hematological features. Thalassemia major is a severe transfusion-dependent anemia. Thalassemia intermedia comprehend a clinically and genotypically very heterogeneous group of thalassemia-like disorders, ranging in severity from the asymptomatic carrier state to the severe transfusion-dependent type. The clinical severity of beta-thalassemia is related to the extent of imbalance between the alpha and nonalpha globin chains. The beta globin ( HBB ) gene maps in the short arm of chromosome 11, in a region containing also the delta globin gene, the embryonic epsilon gene, the fetal A-gamma and G-gamma genes, and a pseudogene (ψB1). Beta-thalassemias are heterogeneous at the molecular level. More than 200 disease-causing mutations have been so far identified. The majority of mutations are single nucleotide substitutions, deletions, or insertions of oligonucleotides leading to frameshift. Rarely, beta-thalassemia results from gross gene deletion. In addition to the variation of the phenotype resulting from allelic heterogeneity at the beta globin locus, the phenotype of beta-thalassemia could also be modified by the action of genetic factors mapping outside the globin gene cluster and not influencing the fetal hemoglobin. Among these factors, the ones best delineated so far are those affecting bilirubin, iron, and bone metabolisms. Because of the high carrier rate for HBB mutations in certain populations and the availability of genetic counseling and prenatal diagnosis, population screening is ongoing in several at-risk populations in the Mediterranean. Population screening associated with genetic counseling was extremely useful by allowing couples at risk to make informed decision on their reproductive choices. Clinical management of thalassemia major consists in regular long-life red blood cell transfusions and iron chelation therapy to remove iron introduced in excess with transfusions. At present, the only definitive cure is bone marrow transplantation. Therapies under investigation are the induction of fetal hemoglobin with pharmacologic compounds and stem cell gene therapy.
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Pitfalls in genetic counselling for β-thalassemia: an individual with 4 different thalassemia mutations
Clinical genetics, 2008Co-Authors: Renzo Galanello, M Furbetta, M. E. Paglietti, Maria Addis, Maria Antonietta Melis, T. Tuveri, Antonio CaoAbstract:This paper describes a complex combination of four thalassemia genes (delta(+), beta(0), nondeletion and deletion Alpha-Thalassemia) in the spouse of a typical high Hb A2 beta-thalassemia carrier presenting for genetic counselling. This complex gene combination resulted in a hematological phenotype, characterized by thalassemia-like red cell indices, normal Hb A2 and Hb F levels and slightly reduced alpha/beta globin chain synthesis ratio, and therefore not indicative for the presence of beta-thalassemia trait. Family studies in combination with alpha-globin gene mapping, haplotype analysis at the beta-globin gene cluster and definition of the beta-thalassemia mutation by oligonucleotide hybridization led us to identify a beta-thalassemia mutation, to define the molecular basis for this phenotype and give the appropriate genetic counselling.
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α-thalassemia carrier identification by DNA analysis in the screening for thalassemia
American journal of hematology, 1998Co-Authors: Renzo Galanello, Carla Sollaino, E. Paglietti, Susanna Barella, Chiara Perra, Ilaria Doneddu, Maria G. Pirroni, L Maccioni, Antonio CaoAbstract:Differentiation between heterozygous Alpha-Thalassemia and several phenotypically resembling alleles at the beta-globin gene cluster such as coinherited delta- and beta-thalassemia or gammadelta beta-thalassemia is a critical step in genetic counseling. In this paper we report our experience in the identification of the Alpha-Thalassemia carrier state using polymerase chain reaction (PCR)-based methods, and the feasibility and simplification of screening for thalassemia using this approach. Alpha-globin genotype was determined by PCR-based method in 526 adult subjects with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), normal hemoglobin A2 and F, and normal serum iron. To verify the reliability of the protocol used, in 68 of these subjects we performed globin chain synthesis analysis and in 101 we determined alpha-globin genotype by Southern blot analysis. Five hundred twenty-one (99%) of 526 subjects examined were identified as carriers of one or two Alpha-Thalassemia alleles. The identification of the Alpha-Thalassemia carrier state may be fast and accurate by PCR-based method, avoiding other cumbersome and expensive methods such as globin chain synthesis and Southern blot analysis.
Pranee Winichagoon - One of the best experts on this subject based on the ideXlab platform.
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Update in Laboratory Diagnosis of Thalassemia.
Frontiers in molecular biosciences, 2020Co-Authors: Thongperm Munkongdee, Ping Chen, Pranee Winichagoon, Suthat Fucharoen, Kittiphong PaiboonsukwongAbstract:Alpha- and β-thalassemias and abnormal hemoglobin (Hb) are common in tropical countries. These abnormal globin genes in different combinations lead to many thalassemic diseases including three severe thalassemia diseases, i.e., homozygous β-thalassemia, β-thalassemia/Hb E, and Hb Bart's hydrops fetalis. Laboratory diagnosis of thalassemia requires a number of tests including red blood cell indices and Hb and DNA analyses. Thalassemic red blood cell analysis with an automated hematology analyzer is a primary screening for thalassemia since microcytosis and decreased Hb content of red blood cells are hallmarks of all thalassemic red blood cells. However, these two red blood cell indices cannot discriminate between thalassemia trait and iron deficiency or between α- and β-thalassemic conditions. Today, Hb analysis may be carried out by either automatic high-performance liquid chromatography (HPLC) or capillary zone electrophoresis (CE) system. These two systems give both qualitative and quantitative analysis of Hb components and help to do thalassemia prenatal and postnatal diagnoses within a short period. Both systems have a good correlation, but the interpretation under the CE system should be done with caution because Hb A2 is clearly separated from Hb E. In case of α-thalassemia gene interaction, it can affect the amount of Hb A2/E. Thalassemia genotypes can be characterized by the intensities between alpha-/beta-globin chains or alpha-/beta-mRNA ratios. However, those are presumptive diagnoses. Only DNA analysis can be made for specific thalassemia mutation diagnosis. Various molecular techniques have been used for point mutation detection in β-thalassemia and large-deletion detection in α-thalassemia. All of these techniques have some advantages and disadvantages. Recently, screening for both α- and β-thalassemia genes by next-generation sequencing (NGS) has been introduced. This technique gives an accurate diagnosis of thalassemia that may be misdiagnosed by other conventional techniques. The major limitation for using NGS in the screening of thalassemia is its cost which is still expensive. All service labs highly recommend to select the technique(s) they are most familiar and most economic one for their routine use.
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Thalassemia and abnormal hemoglobin.
International Journal of Hematology, 2002Co-Authors: Suthat Fucharoen, Pranee WinichagoonAbstract:Thalassemia and abnormal hemoglobins are common genetic disorders in Asia. Thalassemia is not only an important public health problem but also a socio-economic problem of many countries in the region. The approach to deal with the thalassemic problem is to prevent and control birth of new cases. This requires an accurate identification of the couple at high risk for thalassemia. However, the diagnosis of thalassemia carrier states need several tests which are not practical for screening the population at large. Recently we have used two simple laboratory tests to screen for potential thalassemia carriers and hemoglobin E individuals. There is also a new development in using the automatic HPLC to diagnose thalassemic diseases and the carriers. This system gives both qualitative and quantitative analysis of hemoglobin components in the same run with good precision and reproducibility. The system has been applied to study thalassemia and abnormal Hb in adult and cord blood. This system has enabled us to do both prenatal and postnatal diagnosis of thalassemia within the few minutes. However, none of these screening tests can accurately give specific diagnosis of the thalassemia genotype. Specific thalassemia mutation can be carried out by DNA analysis. Many DNA techniques have been used for point mutation detection and small deletion. For the last few years there is a development of DNA chip technology that has been applied for thalassemia mutation as well. Clinically, thalassemia is very heterogeneous in the manifestation. In spite of seemingly identical genotypes, severity of.beta thalassemic patients can vary greatly. Heterogeneity in the clinical manifestation of beta thalassemic diseases may occur from the nature of beta globin gene mutation, alpha thalassemia gene interaction and difference in the amount of Hb F production which is partly associated with a specific beta globin haplotype. However, there is still some beta thalassemia cases that have a mild clinical symptom without those known genetic fators interaction suggesting that there are other additional factors responsible for the mildness of the disease.
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The molecular basis of Alpha-Thalassemia in Thailand.
The Southeast Asian journal of tropical medicine and public health, 1992Co-Authors: Pranee Winichagoon, Fucharoen S, Prawase WasiAbstract:Alpha thalassemia is the most common single gene mutation worldwide. In Thailand there exists 15-30% Alpha-Thalassemia carriers distributed throughout the country. DNA analysis by Southern blot hybridization reveals that the two major Alpha-Thalassemia alleles, Alpha-Thalassemia 1 and Alpha-Thalassemia 2 have different extents of alpha-globin gene deletion. In Alpha-Thalassemia 1, approximately 20 kb of DNA including the two linked alpha 1-and alpha 2-genes are removed and only the alpha-globin gene is intact. Total deletion of the alpha-globin gene cluster is rarely observed. In contrast, only one alpha-globin gene is deleted in Alpha-Thalassemia 2 of which two types have been detected, one involving a deletion of 4.2 kb of DNA (leftward type, -alpha 4.2) and another of 3.7 kb (rightward type, -alpha 3.7); the latter being more common than the former in Thailand. Compound heterozygosity for Alpha-Thalassemia 1 and Alpha-Thalassemia 2 results in HbH disease while homozygosity for Alpha-Thalassemia 1 leads to Hb Bart's hydrops fetalis, the most severe form of thalassemic disease. Three alpha-thalassemic hemoglobinopathies have been detected in Thailand, two of which produce a remarkable reduction in gene product. Upon interacting with Alpha-Thalassemia 1 gene they can lead to HbH disease. The most common in this group is Hb Constant Spring which arises from mutation of the termination codon in the alpha 2-gene resulting in an elongation of the alpha-globin chain.(ABSTRACT TRUNCATED AT 250 WORDS)
Boris E Shmukler - One of the best experts on this subject based on the ideXlab platform.
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genetic disruption of kcc cotransporters in a mouse model of thalassemia intermedia
Blood Cells Molecules and Diseases, 2020Co-Authors: Boris E Shmukler, Alicia Rivera, Parul Bhargava, Katherine Nishimura, Jay Wohlgemuth, James Morton, Michael L Snyder, Lucia De FranceschiAbstract:Abstract β-thalassemia (β-Thal) is caused by defective β-globin production leading to globin chain imbalance, aggregation of free alpha chain in developing erythroblasts, reticulocytes, and mature circulating red blood cells. The hypochromic thalassemic red cells exhibit increased cell dehydration in association with elevated K+ leak and increased K-Cl cotransport activity, each of which has been linked to globin chain imbalance and related oxidative stress. We therefore tested the effect of genetic inactivation of K-Cl cotransporters KCC1 and KCC3 in a mouse model of β-thalassemia intermedia. In the absence of these transporters, the anemia of β-Thal mice was ameliorated, in association with increased MCV and reductions in CHCM and hyperdense cells, as well as in spleen size. The resting K+ content of β-Thal red cells was greatly increased, and Thal-associated splenomegaly slightly decreased. Lack of KCC1 and KCC3 activity in Thal red cells reduced red cell density and improved β-Thal-associated osmotic fragility. We conclude that genetic inactivation of K-Cl cotransport can reverse red cell dehydration and partially attenuate the hematologic phenotype in a mouse model of β-thalassemia.
Antonio Cao - One of the best experts on this subject based on the ideXlab platform.
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Pitfalls in genetic counselling for β-thalassemia: an individual with 4 different thalassemia mutations
Clinical genetics, 2008Co-Authors: Renzo Galanello, M Furbetta, M. E. Paglietti, Maria Addis, Maria Antonietta Melis, T. Tuveri, Antonio CaoAbstract:This paper describes a complex combination of four thalassemia genes (delta(+), beta(0), nondeletion and deletion Alpha-Thalassemia) in the spouse of a typical high Hb A2 beta-thalassemia carrier presenting for genetic counselling. This complex gene combination resulted in a hematological phenotype, characterized by thalassemia-like red cell indices, normal Hb A2 and Hb F levels and slightly reduced alpha/beta globin chain synthesis ratio, and therefore not indicative for the presence of beta-thalassemia trait. Family studies in combination with alpha-globin gene mapping, haplotype analysis at the beta-globin gene cluster and definition of the beta-thalassemia mutation by oligonucleotide hybridization led us to identify a beta-thalassemia mutation, to define the molecular basis for this phenotype and give the appropriate genetic counselling.
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α-thalassemia carrier identification by DNA analysis in the screening for thalassemia
American journal of hematology, 1998Co-Authors: Renzo Galanello, Carla Sollaino, E. Paglietti, Susanna Barella, Chiara Perra, Ilaria Doneddu, Maria G. Pirroni, L Maccioni, Antonio CaoAbstract:Differentiation between heterozygous Alpha-Thalassemia and several phenotypically resembling alleles at the beta-globin gene cluster such as coinherited delta- and beta-thalassemia or gammadelta beta-thalassemia is a critical step in genetic counseling. In this paper we report our experience in the identification of the Alpha-Thalassemia carrier state using polymerase chain reaction (PCR)-based methods, and the feasibility and simplification of screening for thalassemia using this approach. Alpha-globin genotype was determined by PCR-based method in 526 adult subjects with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), normal hemoglobin A2 and F, and normal serum iron. To verify the reliability of the protocol used, in 68 of these subjects we performed globin chain synthesis analysis and in 101 we determined alpha-globin genotype by Southern blot analysis. Five hundred twenty-one (99%) of 526 subjects examined were identified as carriers of one or two Alpha-Thalassemia alleles. The identification of the Alpha-Thalassemia carrier state may be fast and accurate by PCR-based method, avoiding other cumbersome and expensive methods such as globin chain synthesis and Southern blot analysis.
Kittiphong Paiboonsukwong - One of the best experts on this subject based on the ideXlab platform.
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Update in Laboratory Diagnosis of Thalassemia.
Frontiers in molecular biosciences, 2020Co-Authors: Thongperm Munkongdee, Ping Chen, Pranee Winichagoon, Suthat Fucharoen, Kittiphong PaiboonsukwongAbstract:Alpha- and β-thalassemias and abnormal hemoglobin (Hb) are common in tropical countries. These abnormal globin genes in different combinations lead to many thalassemic diseases including three severe thalassemia diseases, i.e., homozygous β-thalassemia, β-thalassemia/Hb E, and Hb Bart's hydrops fetalis. Laboratory diagnosis of thalassemia requires a number of tests including red blood cell indices and Hb and DNA analyses. Thalassemic red blood cell analysis with an automated hematology analyzer is a primary screening for thalassemia since microcytosis and decreased Hb content of red blood cells are hallmarks of all thalassemic red blood cells. However, these two red blood cell indices cannot discriminate between thalassemia trait and iron deficiency or between α- and β-thalassemic conditions. Today, Hb analysis may be carried out by either automatic high-performance liquid chromatography (HPLC) or capillary zone electrophoresis (CE) system. These two systems give both qualitative and quantitative analysis of Hb components and help to do thalassemia prenatal and postnatal diagnoses within a short period. Both systems have a good correlation, but the interpretation under the CE system should be done with caution because Hb A2 is clearly separated from Hb E. In case of α-thalassemia gene interaction, it can affect the amount of Hb A2/E. Thalassemia genotypes can be characterized by the intensities between alpha-/beta-globin chains or alpha-/beta-mRNA ratios. However, those are presumptive diagnoses. Only DNA analysis can be made for specific thalassemia mutation diagnosis. Various molecular techniques have been used for point mutation detection in β-thalassemia and large-deletion detection in α-thalassemia. All of these techniques have some advantages and disadvantages. Recently, screening for both α- and β-thalassemia genes by next-generation sequencing (NGS) has been introduced. This technique gives an accurate diagnosis of thalassemia that may be misdiagnosed by other conventional techniques. The major limitation for using NGS in the screening of thalassemia is its cost which is still expensive. All service labs highly recommend to select the technique(s) they are most familiar and most economic one for their routine use.
