Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain
- Autores
- Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Targovnik, Hector Manuel; García, Eliana; Veber, Ernesto Samuel; Crisp, Renée; Elena, Graciela; Varela, Viviana; Fornasari, Maria Silvina
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in-frame deletions, leading to β-globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α-helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia.
Fil: Scheps, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Hasenahuer, Marcia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: García, Eliana. Hospital Nacional “Profesor Alejandro Posadas”; Argentina
Fil: Veber, Ernesto Samuel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Crisp, Renée. Hospital Nacional “Profesor Alejandro Posadas”; Argentina
Fil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Varela, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina - Materia
-
BIOINFORMATICS
DOMINANT BETA-THALASSEMIA
HBB GENE
HEMOLYTIC ANEMIA
UNSTABLE HEMOGLOBIN VARIANTS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/86096
Ver los metadatos del registro completo
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Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chainScheps, KarenHasenahuer, Marcia AnahíParisi, Gustavo DanielTargovnik, Hector ManuelGarcía, ElianaVeber, Ernesto SamuelCrisp, RenéeElena, GracielaVarela, VivianaFornasari, Maria SilvinaBIOINFORMATICSDOMINANT BETA-THALASSEMIAHBB GENEHEMOLYTIC ANEMIAUNSTABLE HEMOGLOBIN VARIANTShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in-frame deletions, leading to β-globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α-helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia.Fil: Scheps, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Hasenahuer, Marcia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: García, Eliana. Hospital Nacional “Profesor Alejandro Posadas”; ArgentinaFil: Veber, Ernesto Samuel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Crisp, Renée. Hospital Nacional “Profesor Alejandro Posadas”; ArgentinaFil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Varela, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaWiley Blackwell Publishing, Inc2018-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86096Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Targovnik, Hector Manuel; García, Eliana; et al.; Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain; Wiley Blackwell Publishing, Inc; European Journal Of Haematology; 100; 6; 6-2018; 529-5350902-4441CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/ejh.13029info:eu-repo/semantics/altIdentifier/doi/10.1111/ejh.13029info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:47:21Zoai:ri.conicet.gov.ar:11336/86096instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:47:21.89CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
title |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
spellingShingle |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain Scheps, Karen BIOINFORMATICS DOMINANT BETA-THALASSEMIA HBB GENE HEMOLYTIC ANEMIA UNSTABLE HEMOGLOBIN VARIANTS |
title_short |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
title_full |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
title_fullStr |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
title_full_unstemmed |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
title_sort |
Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain |
dc.creator.none.fl_str_mv |
Scheps, Karen Hasenahuer, Marcia Anahí Parisi, Gustavo Daniel Targovnik, Hector Manuel García, Eliana Veber, Ernesto Samuel Crisp, Renée Elena, Graciela Varela, Viviana Fornasari, Maria Silvina |
author |
Scheps, Karen |
author_facet |
Scheps, Karen Hasenahuer, Marcia Anahí Parisi, Gustavo Daniel Targovnik, Hector Manuel García, Eliana Veber, Ernesto Samuel Crisp, Renée Elena, Graciela Varela, Viviana Fornasari, Maria Silvina |
author_role |
author |
author2 |
Hasenahuer, Marcia Anahí Parisi, Gustavo Daniel Targovnik, Hector Manuel García, Eliana Veber, Ernesto Samuel Crisp, Renée Elena, Graciela Varela, Viviana Fornasari, Maria Silvina |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
BIOINFORMATICS DOMINANT BETA-THALASSEMIA HBB GENE HEMOLYTIC ANEMIA UNSTABLE HEMOGLOBIN VARIANTS |
topic |
BIOINFORMATICS DOMINANT BETA-THALASSEMIA HBB GENE HEMOLYTIC ANEMIA UNSTABLE HEMOGLOBIN VARIANTS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in-frame deletions, leading to β-globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α-helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia. Fil: Scheps, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Hasenahuer, Marcia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: García, Eliana. Hospital Nacional “Profesor Alejandro Posadas”; Argentina Fil: Veber, Ernesto Samuel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Crisp, Renée. Hospital Nacional “Profesor Alejandro Posadas”; Argentina Fil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina Fil: Varela, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina Fil: Fornasari, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina |
description |
Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in-frame deletions, leading to β-globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α-helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-06 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/86096 Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Targovnik, Hector Manuel; García, Eliana; et al.; Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain; Wiley Blackwell Publishing, Inc; European Journal Of Haematology; 100; 6; 6-2018; 529-535 0902-4441 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/86096 |
identifier_str_mv |
Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Targovnik, Hector Manuel; García, Eliana; et al.; Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain; Wiley Blackwell Publishing, Inc; European Journal Of Haematology; 100; 6; 6-2018; 529-535 0902-4441 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/ejh.13029 info:eu-repo/semantics/altIdentifier/doi/10.1111/ejh.13029 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614517316648960 |
score |
13.070432 |