HEMOGLOBINOPATHIES WITH LEVELS HBA2 DECREASED. DELTA GENE MUTATIONS FOUND IN A SPANISH CENTER.
(Abstract release date: 05/19/16)
EHA Library. Ropero P. 06/09/16; 133022; E1473
Dr. Paloma Ropero
Contributions
Contributions
Abstract
Abstract: E1473
Type: Eposter Presentation
Background
HbA2 reaches its final value (2.5% -3.5%) in the first year of life. Due to this low expression and the lack of significant pathology, HbA2 is not considered relevant, but mutations in the δ gene can cause δ-thalassemia and Hb variants of δ chain are interesting because they interfere in HbA2 quantification. HbA2 consists of chains of α globin and δ; therefore, alterations in any of these genes may influence HbA2 levels.
Aims
We present structural hemoglobinopathies and thalassemias that present with decreased levels of HbA2, as well as the first compilation of mutations in the gene δ globin, found in Spain.
Methods
The 208 patients that were analyzed presented HbA2 values below 2.5% and microcytic and hypochromic or normocytic and normochromic without iron deficiency anemia. HbA2 and HbF levels, as well as the different hemoglobins, were measured and analyzed by ion-exchange HPLC (VARIANTTM II). Hemoglobins were studied by capillary zone electrophoresis (CE) (Sebia) and globin chains by reverse-phase HPLC. Genetic analysis of the α and δ genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR.
Results
In α-thalassemia (n=94), HbA2 levels ranged from 1.39 to 2.43%; in δ-thalassemia (n=5), HbA2 levels researched in δ+-thalassemia 1.77% and for δ0-thalassemiain 1.70%; in δβ-thalassemia (n=13), homozygosity resulted in undetectable HbA2 levels. Structural hemoglobinopathies (n=96), all heterozygous, in the α chain (n=84) and δ chain (n=12) had HbA2 rates of 1.76% and 1.75%, respectively.
Conclusion
208 samples, with HbA2<2.5%, showed α gene or δ globin anomalies of quantitative (thalassemia) or qualitative (structural hemoglobinopathies). In the α-thalassemia, the greatest loss of genes corresponds to the lowest levels of HbA2, since α genes are preferably combined to form the β HbA. The heterozygous δ +-thalassemia had higher levels than δ0-thalassemia. It should be suspected of a δ-thalassemia when, in normal and without iron deficiency, HbA2 levels are lower than the 2%., in these cases the direct sequencing of the gene δ, it will reveal a point mutation in homozygous or heterozygous state. In the δβ-thalassemia, homozygosity no levels of HbA2.The decrease in levels of HbA2 in α chain hemoglobinopathies is owing to a new α globin chain (αX) because its variant corresponding HbA2 (α2Xδ2) is formed. The greater decrease corresponds to homozygosity, because there is less αA globin chain synthesis, regardless of the mutated gene (α1 or α2). In this work we have identified five variants of δ chain because they are relatively common and generally easy to detect not only because halved the HbA2 value, but because they often show a second fraction of HbA2 almost the same expression, whether prior or after normal HbA2. The variant HbA2-Madrid was first described in the literature.HbA2 is an essential parameter in the differential diagnosis of thalassemia. Using the HPLC and EC provide not only the quantification of HbA2 but also information other hemoglobins, so the same analysis helps identify hemoglobin variants of either strand and detect thalassemias not otherwise It has been possible diagnosis, avoiding that risk couples may be advised incorrectly.
Session topic: E-poster
Keyword(s): Hemoglobin variants, Thalassemia
Type: Eposter Presentation
Background
HbA2 reaches its final value (2.5% -3.5%) in the first year of life. Due to this low expression and the lack of significant pathology, HbA2 is not considered relevant, but mutations in the δ gene can cause δ-thalassemia and Hb variants of δ chain are interesting because they interfere in HbA2 quantification. HbA2 consists of chains of α globin and δ; therefore, alterations in any of these genes may influence HbA2 levels.
Aims
We present structural hemoglobinopathies and thalassemias that present with decreased levels of HbA2, as well as the first compilation of mutations in the gene δ globin, found in Spain.
Methods
The 208 patients that were analyzed presented HbA2 values below 2.5% and microcytic and hypochromic or normocytic and normochromic without iron deficiency anemia. HbA2 and HbF levels, as well as the different hemoglobins, were measured and analyzed by ion-exchange HPLC (VARIANTTM II). Hemoglobins were studied by capillary zone electrophoresis (CE) (Sebia) and globin chains by reverse-phase HPLC. Genetic analysis of the α and δ genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR.
Results
In α-thalassemia (n=94), HbA2 levels ranged from 1.39 to 2.43%; in δ-thalassemia (n=5), HbA2 levels researched in δ+-thalassemia 1.77% and for δ0-thalassemiain 1.70%; in δβ-thalassemia (n=13), homozygosity resulted in undetectable HbA2 levels. Structural hemoglobinopathies (n=96), all heterozygous, in the α chain (n=84) and δ chain (n=12) had HbA2 rates of 1.76% and 1.75%, respectively.
Conclusion
208 samples, with HbA2<2.5%, showed α gene or δ globin anomalies of quantitative (thalassemia) or qualitative (structural hemoglobinopathies). In the α-thalassemia, the greatest loss of genes corresponds to the lowest levels of HbA2, since α genes are preferably combined to form the β HbA. The heterozygous δ +-thalassemia had higher levels than δ0-thalassemia. It should be suspected of a δ-thalassemia when, in normal and without iron deficiency, HbA2 levels are lower than the 2%., in these cases the direct sequencing of the gene δ, it will reveal a point mutation in homozygous or heterozygous state. In the δβ-thalassemia, homozygosity no levels of HbA2.The decrease in levels of HbA2 in α chain hemoglobinopathies is owing to a new α globin chain (αX) because its variant corresponding HbA2 (α2Xδ2) is formed. The greater decrease corresponds to homozygosity, because there is less αA globin chain synthesis, regardless of the mutated gene (α1 or α2). In this work we have identified five variants of δ chain because they are relatively common and generally easy to detect not only because halved the HbA2 value, but because they often show a second fraction of HbA2 almost the same expression, whether prior or after normal HbA2. The variant HbA2-Madrid was first described in the literature.HbA2 is an essential parameter in the differential diagnosis of thalassemia. Using the HPLC and EC provide not only the quantification of HbA2 but also information other hemoglobins, so the same analysis helps identify hemoglobin variants of either strand and detect thalassemias not otherwise It has been possible diagnosis, avoiding that risk couples may be advised incorrectly.
Session topic: E-poster
Keyword(s): Hemoglobin variants, Thalassemia
Abstract: E1473
Type: Eposter Presentation
Background
HbA2 reaches its final value (2.5% -3.5%) in the first year of life. Due to this low expression and the lack of significant pathology, HbA2 is not considered relevant, but mutations in the δ gene can cause δ-thalassemia and Hb variants of δ chain are interesting because they interfere in HbA2 quantification. HbA2 consists of chains of α globin and δ; therefore, alterations in any of these genes may influence HbA2 levels.
Aims
We present structural hemoglobinopathies and thalassemias that present with decreased levels of HbA2, as well as the first compilation of mutations in the gene δ globin, found in Spain.
Methods
The 208 patients that were analyzed presented HbA2 values below 2.5% and microcytic and hypochromic or normocytic and normochromic without iron deficiency anemia. HbA2 and HbF levels, as well as the different hemoglobins, were measured and analyzed by ion-exchange HPLC (VARIANTTM II). Hemoglobins were studied by capillary zone electrophoresis (CE) (Sebia) and globin chains by reverse-phase HPLC. Genetic analysis of the α and δ genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR.
Results
In α-thalassemia (n=94), HbA2 levels ranged from 1.39 to 2.43%; in δ-thalassemia (n=5), HbA2 levels researched in δ+-thalassemia 1.77% and for δ0-thalassemiain 1.70%; in δβ-thalassemia (n=13), homozygosity resulted in undetectable HbA2 levels. Structural hemoglobinopathies (n=96), all heterozygous, in the α chain (n=84) and δ chain (n=12) had HbA2 rates of 1.76% and 1.75%, respectively.
Conclusion
208 samples, with HbA2<2.5%, showed α gene or δ globin anomalies of quantitative (thalassemia) or qualitative (structural hemoglobinopathies). In the α-thalassemia, the greatest loss of genes corresponds to the lowest levels of HbA2, since α genes are preferably combined to form the β HbA. The heterozygous δ +-thalassemia had higher levels than δ0-thalassemia. It should be suspected of a δ-thalassemia when, in normal and without iron deficiency, HbA2 levels are lower than the 2%., in these cases the direct sequencing of the gene δ, it will reveal a point mutation in homozygous or heterozygous state. In the δβ-thalassemia, homozygosity no levels of HbA2.The decrease in levels of HbA2 in α chain hemoglobinopathies is owing to a new α globin chain (αX) because its variant corresponding HbA2 (α2Xδ2) is formed. The greater decrease corresponds to homozygosity, because there is less αA globin chain synthesis, regardless of the mutated gene (α1 or α2). In this work we have identified five variants of δ chain because they are relatively common and generally easy to detect not only because halved the HbA2 value, but because they often show a second fraction of HbA2 almost the same expression, whether prior or after normal HbA2. The variant HbA2-Madrid was first described in the literature.HbA2 is an essential parameter in the differential diagnosis of thalassemia. Using the HPLC and EC provide not only the quantification of HbA2 but also information other hemoglobins, so the same analysis helps identify hemoglobin variants of either strand and detect thalassemias not otherwise It has been possible diagnosis, avoiding that risk couples may be advised incorrectly.
Session topic: E-poster
Keyword(s): Hemoglobin variants, Thalassemia
Type: Eposter Presentation
Background
HbA2 reaches its final value (2.5% -3.5%) in the first year of life. Due to this low expression and the lack of significant pathology, HbA2 is not considered relevant, but mutations in the δ gene can cause δ-thalassemia and Hb variants of δ chain are interesting because they interfere in HbA2 quantification. HbA2 consists of chains of α globin and δ; therefore, alterations in any of these genes may influence HbA2 levels.
Aims
We present structural hemoglobinopathies and thalassemias that present with decreased levels of HbA2, as well as the first compilation of mutations in the gene δ globin, found in Spain.
Methods
The 208 patients that were analyzed presented HbA2 values below 2.5% and microcytic and hypochromic or normocytic and normochromic without iron deficiency anemia. HbA2 and HbF levels, as well as the different hemoglobins, were measured and analyzed by ion-exchange HPLC (VARIANTTM II). Hemoglobins were studied by capillary zone electrophoresis (CE) (Sebia) and globin chains by reverse-phase HPLC. Genetic analysis of the α and δ genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR.
Results
In α-thalassemia (n=94), HbA2 levels ranged from 1.39 to 2.43%; in δ-thalassemia (n=5), HbA2 levels researched in δ+-thalassemia 1.77% and for δ0-thalassemiain 1.70%; in δβ-thalassemia (n=13), homozygosity resulted in undetectable HbA2 levels. Structural hemoglobinopathies (n=96), all heterozygous, in the α chain (n=84) and δ chain (n=12) had HbA2 rates of 1.76% and 1.75%, respectively.
Conclusion
208 samples, with HbA2<2.5%, showed α gene or δ globin anomalies of quantitative (thalassemia) or qualitative (structural hemoglobinopathies). In the α-thalassemia, the greatest loss of genes corresponds to the lowest levels of HbA2, since α genes are preferably combined to form the β HbA. The heterozygous δ +-thalassemia had higher levels than δ0-thalassemia. It should be suspected of a δ-thalassemia when, in normal and without iron deficiency, HbA2 levels are lower than the 2%., in these cases the direct sequencing of the gene δ, it will reveal a point mutation in homozygous or heterozygous state. In the δβ-thalassemia, homozygosity no levels of HbA2.The decrease in levels of HbA2 in α chain hemoglobinopathies is owing to a new α globin chain (αX) because its variant corresponding HbA2 (α2Xδ2) is formed. The greater decrease corresponds to homozygosity, because there is less αA globin chain synthesis, regardless of the mutated gene (α1 or α2). In this work we have identified five variants of δ chain because they are relatively common and generally easy to detect not only because halved the HbA2 value, but because they often show a second fraction of HbA2 almost the same expression, whether prior or after normal HbA2. The variant HbA2-Madrid was first described in the literature.HbA2 is an essential parameter in the differential diagnosis of thalassemia. Using the HPLC and EC provide not only the quantification of HbA2 but also information other hemoglobins, so the same analysis helps identify hemoglobin variants of either strand and detect thalassemias not otherwise It has been possible diagnosis, avoiding that risk couples may be advised incorrectly.
Session topic: E-poster
Keyword(s): Hemoglobin variants, Thalassemia
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