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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/86096
Acceder
id CONICETDig_71c38548943b9cc8e1f80bc47db0121a
oai_identifier_str oai:ri.conicet.gov.ar:11336/86096
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-29T12:55:15Zoai: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:34982025-10-29 12:55:15.615CONICET 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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score 13.10058

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