β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain
ObjectivesTo verify with hematimetric data that the diagnosis and clinical grade of β-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous β-thalassemia coexist.Materials and MethodsRetrospective study in which 73 patients of Caucasian origin participated, who simu...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-03-01
|
| Series: | Frontiers in Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.866396/full |
| _version_ | 1818311310992998400 |
|---|---|
| author | Paloma Ropero Paloma Ropero Fernando Ataúlfo González Fernández Jorge M. Nieto Jorge M. Nieto Williana Melissa Torres-Jiménez Celina Benavente |
| author_facet | Paloma Ropero Paloma Ropero Fernando Ataúlfo González Fernández Jorge M. Nieto Jorge M. Nieto Williana Melissa Torres-Jiménez Celina Benavente |
| author_sort | Paloma Ropero |
| collection | DOAJ |
| description | ObjectivesTo verify with hematimetric data that the diagnosis and clinical grade of β-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous β-thalassemia coexist.Materials and MethodsRetrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a triplication or quadruplication of genes α and β-thalassemia.Screening for the most frequent α-thalassemia mutations as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization with a commercial Alpha-Globin StripAssay kit and confirmed by MLPA (Multiplex ligation-dependent probe amplification). The molecular diagnosis of β-thalassemia was carried out by automatic sequencing according to the Sanger method.ResultsThe genotypes have been classified into three groups according to the number of α globin genes and the severity of the alteration in the β globin gene. All had a mutation in the HBB gene (β0-thalassemia, β+-thalassemia severe, and β+-thalassemia mild). Group I patients who have coherent 6 α genes and groups II and III with 5 α globin genes. In group III, the patients were carriers of mutations affecting the β and δ globin genes. The most significant hematological parameters were hemoglobin levels, MCV, RDW, and the percentage of Hb F.ConclusionsIn group I, regardless of the distribution of the 6 α globin genes, homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), the association with heterozygous β-thalassemia results in severe to moderate anemia that may or may not require transfusion therapy, is the severity of the HBB gene mutation that would determine the clinical variation. Group II patients phenotypically behaved like mild thalassemia intermedia, except for one case that presented thalassemic trait because it also presented an associated α-thalassemia (ααα/-α3.7). Finally, group III patients behaved as a thalassemic trait since all were carriers of mutations that increase the overexpression of γ genes. |
| first_indexed | 2024-12-13T07:59:56Z |
| format | Article |
| id | doaj.art-0d431a33d3bd49f4ae7b9a467577ab04 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-13T07:59:56Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-0d431a33d3bd49f4ae7b9a467577ab042022-12-21T23:54:28ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-03-01910.3389/fmed.2022.866396866396β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in SpainPaloma Ropero0Paloma Ropero1Fernando Ataúlfo González Fernández2Jorge M. Nieto3Jorge M. Nieto4Williana Melissa Torres-Jiménez5Celina Benavente6Hematology Service, Hospital Clínico San Carlos, Madrid, SpainInstituto de Investigación Sanitaria Hospital Clínico San Carlos, Madrid, SpainHematology Service, Hospital Clínico San Carlos, Madrid, SpainHematology Service, Hospital Clínico San Carlos, Madrid, SpainInstituto de Investigación Sanitaria Hospital Clínico San Carlos, Madrid, SpainHematology Service, Hospital Virgen de La Luz, Cuenca, SpainHematology Service, Hospital Clínico San Carlos, Madrid, SpainObjectivesTo verify with hematimetric data that the diagnosis and clinical grade of β-TI can be established when a triplication of alpha genes (αααanti 3.7) and heterozygous β-thalassemia coexist.Materials and MethodsRetrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a triplication or quadruplication of genes α and β-thalassemia.Screening for the most frequent α-thalassemia mutations as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization with a commercial Alpha-Globin StripAssay kit and confirmed by MLPA (Multiplex ligation-dependent probe amplification). The molecular diagnosis of β-thalassemia was carried out by automatic sequencing according to the Sanger method.ResultsThe genotypes have been classified into three groups according to the number of α globin genes and the severity of the alteration in the β globin gene. All had a mutation in the HBB gene (β0-thalassemia, β+-thalassemia severe, and β+-thalassemia mild). Group I patients who have coherent 6 α genes and groups II and III with 5 α globin genes. In group III, the patients were carriers of mutations affecting the β and δ globin genes. The most significant hematological parameters were hemoglobin levels, MCV, RDW, and the percentage of Hb F.ConclusionsIn group I, regardless of the distribution of the 6 α globin genes, homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), the association with heterozygous β-thalassemia results in severe to moderate anemia that may or may not require transfusion therapy, is the severity of the HBB gene mutation that would determine the clinical variation. Group II patients phenotypically behaved like mild thalassemia intermedia, except for one case that presented thalassemic trait because it also presented an associated α-thalassemia (ααα/-α3.7). Finally, group III patients behaved as a thalassemic trait since all were carriers of mutations that increase the overexpression of γ genes.https://www.frontiersin.org/articles/10.3389/fmed.2022.866396/fullbeta thalassemia intermediatriplication alpha genesbeta thalassemiamolecular diagnosisphenotype |
| spellingShingle | Paloma Ropero Paloma Ropero Fernando Ataúlfo González Fernández Jorge M. Nieto Jorge M. Nieto Williana Melissa Torres-Jiménez Celina Benavente β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain Frontiers in Medicine beta thalassemia intermedia triplication alpha genes beta thalassemia molecular diagnosis phenotype |
| title | β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain |
| title_full | β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain |
| title_fullStr | β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain |
| title_full_unstemmed | β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain |
| title_short | β-Thalassemia Intermedia: Interaction of α-Globin Gene Triplication With β-thalassemia Heterozygous in Spain |
| title_sort | β thalassemia intermedia interaction of α globin gene triplication with β thalassemia heterozygous in spain |
| topic | beta thalassemia intermedia triplication alpha genes beta thalassemia molecular diagnosis phenotype |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.866396/full |
| work_keys_str_mv | AT palomaropero bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain AT palomaropero bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain AT fernandoataulfogonzalezfernandez bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain AT jorgemnieto bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain AT jorgemnieto bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain AT willianamelissatorresjimenez bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain AT celinabenavente bthalassemiaintermediainteractionofaglobingenetriplicationwithbthalassemiaheterozygousinspain |