Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia

Autores
Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Fornasari, Maria Silvina; Pennesi, Sandra P.; Erramouspe, Beatriz; Basack, Felisa N.; Veber, Ernesto S.; Aversa, Luis; Elena, Graciela; Varela, Viviana
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant b-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB: c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated b-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated b-globins would affect the formation of the ab dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.
Fil: Scheps, Karen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Hasenahuer, Marcia Anahí. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Pennesi, Sandra P.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; Argentina
Fil: Erramouspe, Beatriz. Unidad Asistencial "Dr. César Milstein"; Argentina
Fil: Basack, Felisa N.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; Argentina
Fil: Veber, Ernesto S.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Aversa, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; Argentina
Fil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Varela, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Materia
elongated beta-globin
protein structure
dominant beta-thalassemia
frameshift mutations
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:11336/105265
Acceder
id CONICETDig_c69d6881b0eefcf2b851df7de15834a8
oai_identifier_str oai:ri.conicet.gov.ar:11336/105265
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemiaScheps, KarenHasenahuer, Marcia AnahíParisi, Gustavo DanielFornasari, Maria SilvinaPennesi, Sandra P.Erramouspe, BeatrizBasack, Felisa N.Veber, Ernesto S.Aversa, LuisElena, GracielaVarela, Vivianaelongated beta-globinprotein structuredominant beta-thalassemiaframeshift mutationshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3https://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant b-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB: c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated b-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated b-globins would affect the formation of the ab dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.Fil: Scheps, Karen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Hasenahuer, Marcia Anahí. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Pennesi, Sandra P.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; ArgentinaFil: Erramouspe, Beatriz. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Basack, Felisa N.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; ArgentinaFil: Veber, Ernesto S.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Aversa, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; ArgentinaFil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Varela, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaWiley2014-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/105265Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Fornasari, Maria Silvina; Pennesi, Sandra P.; et al.; Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia; Wiley; European Journal Of Haematology; 94; 10-2014; 498-5031600-0609CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/ejh.12456/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/ejh.12456info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:00Zoai:ri.conicet.gov.ar:11336/105265instacron: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:34982025-09-03 09:49:01.366CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
title Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
spellingShingle Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
Scheps, Karen
elongated beta-globin
protein structure
dominant beta-thalassemia
frameshift mutations
title_short Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
title_full Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
title_fullStr Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
title_full_unstemmed Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
title_sort Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
dc.creator.none.fl_str_mv Scheps, Karen
Hasenahuer, Marcia Anahí
Parisi, Gustavo Daniel
Fornasari, Maria Silvina
Pennesi, Sandra P.
Erramouspe, Beatriz
Basack, Felisa N.
Veber, Ernesto S.
Aversa, Luis
Elena, Graciela
Varela, Viviana
author Scheps, Karen
author_facet Scheps, Karen
Hasenahuer, Marcia Anahí
Parisi, Gustavo Daniel
Fornasari, Maria Silvina
Pennesi, Sandra P.
Erramouspe, Beatriz
Basack, Felisa N.
Veber, Ernesto S.
Aversa, Luis
Elena, Graciela
Varela, Viviana
author_role author
author2 Hasenahuer, Marcia Anahí
Parisi, Gustavo Daniel
Fornasari, Maria Silvina
Pennesi, Sandra P.
Erramouspe, Beatriz
Basack, Felisa N.
Veber, Ernesto S.
Aversa, Luis
Elena, Graciela
Varela, Viviana
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv elongated beta-globin
protein structure
dominant beta-thalassemia
frameshift mutations
topic elongated beta-globin
protein structure
dominant beta-thalassemia
frameshift mutations
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant b-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB: c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated b-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated b-globins would affect the formation of the ab dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.
Fil: Scheps, Karen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
Fil: Hasenahuer, Marcia Anahí. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina
Fil: Pennesi, Sandra P.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; Argentina
Fil: Erramouspe, Beatriz. Unidad Asistencial "Dr. César Milstein"; Argentina
Fil: Basack, Felisa N.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; Argentina
Fil: Veber, Ernesto S.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Aversa, Luis. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio Hematología; Argentina
Fil: Elena, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina
Fil: Varela, Viviana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina
description We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant b-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB: c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated b-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated b-globins would affect the formation of the ab dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.
publishDate 2014
dc.date.none.fl_str_mv 2014-10
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/11336/105265
Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Fornasari, Maria Silvina; Pennesi, Sandra P.; et al.; Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia; Wiley; European Journal Of Haematology; 94; 10-2014; 498-503
1600-0609
CONICET Digital
CONICET
url http://hdl.handle.net/11336/105265
identifier_str_mv Scheps, Karen; Hasenahuer, Marcia Anahí; Parisi, Gustavo Daniel; Fornasari, Maria Silvina; Pennesi, Sandra P.; et al.; Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia; Wiley; European Journal Of Haematology; 94; 10-2014; 498-503
1600-0609
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/ejh.12456/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/ejh.12456
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
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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
_version_ 1842268949315584000
score 13.13397

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