Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation

Autores
Abelleyro, Miguel Martin; Marchione, Vanina Daniela; Elhelou, L.; Radic, Claudia Pamela; Rossetti, Liliana Carmen; Nemec, Diego Martín; de Brasi, Carlos Daniel
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Large F8 deletions cause 10-15% of severe-Haemophilia A (HA) cases and associate with the highest clinical/biochemical severity and with significantly augmented risks for developing inhibitors against therapeutic FVIII. Only 45-50% of severe-HA cases present family history of the disease. In the remnant cases (sporadic-HA), the mutation origin defines different clinical scenarios in which the risk of recurrence and thus genetic counselling significantly vary. The origin of the causative mutation may be either pre-zygotic or post-zygotic generating a genetic mosaicism affecting, partially or totally, one or more tissue/organs including the gonads. Furthermore, the technical features of the genotyping approach for detecting and measuring an eventual genetic mosaicism critically affect its diagnosis. The quali-quantitative extent of somatic and germinal mosaicisms is passively assumed to be associated with the phenotypic expression of haemophilia severity and inheritance pattern, respectively. We present a case of a family affected with HA in which the clinical/biochemical severity and inheritance patterns associate with the observed fraction of mosaic cells bearing a F8-promoter deletion.
Fil: Abelleyro, Miguel Martin. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Marchione, Vanina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Elhelou, L.. Fundacion de la Hemofilia; Argentina
Fil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Rossetti, Liliana Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Nemec, Diego Martín. Fundacion de la Hemofilia; Argentina
Fil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Materia
F8
Hemophilia
Mosaicism
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:11336/96383
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/96383
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype QuantitationAbelleyro, Miguel MartinMarchione, Vanina DanielaElhelou, L.Radic, Claudia PamelaRossetti, Liliana CarmenNemec, Diego Martínde Brasi, Carlos DanielF8HemophiliaMosaicismhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Large F8 deletions cause 10-15% of severe-Haemophilia A (HA) cases and associate with the highest clinical/biochemical severity and with significantly augmented risks for developing inhibitors against therapeutic FVIII. Only 45-50% of severe-HA cases present family history of the disease. In the remnant cases (sporadic-HA), the mutation origin defines different clinical scenarios in which the risk of recurrence and thus genetic counselling significantly vary. The origin of the causative mutation may be either pre-zygotic or post-zygotic generating a genetic mosaicism affecting, partially or totally, one or more tissue/organs including the gonads. Furthermore, the technical features of the genotyping approach for detecting and measuring an eventual genetic mosaicism critically affect its diagnosis. The quali-quantitative extent of somatic and germinal mosaicisms is passively assumed to be associated with the phenotypic expression of haemophilia severity and inheritance pattern, respectively. We present a case of a family affected with HA in which the clinical/biochemical severity and inheritance patterns associate with the observed fraction of mosaic cells bearing a F8-promoter deletion.Fil: Abelleyro, Miguel Martin. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Marchione, Vanina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Elhelou, L.. Fundacion de la Hemofilia; ArgentinaFil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Rossetti, Liliana Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Nemec, Diego Martín. Fundacion de la Hemofilia; ArgentinaFil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; ArgentinaThieme Medical Publ Inc2018-03info: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/11336/96383Abelleyro, Miguel Martin; Marchione, Vanina Daniela; Elhelou, L.; Radic, Claudia Pamela; Rossetti, Liliana Carmen; et al.; Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation; Thieme Medical Publ Inc; Thrombosis and Haemostasis; 118; 3; 3-2018; 617-6200340-6245CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://europepmc.org/article/med/29534251info:eu-repo/semantics/altIdentifier/doi/10.1055/s-0038-1623536info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0038-1623536info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:20Zoai:ri.conicet.gov.ar:11336/96383instacron: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 09:48:20.767CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
title Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
spellingShingle Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
Abelleyro, Miguel Martin
F8
Hemophilia
Mosaicism
title_short Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
title_full Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
title_fullStr Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
title_full_unstemmed Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
title_sort Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation
dc.creator.none.fl_str_mv Abelleyro, Miguel Martin
Marchione, Vanina Daniela
Elhelou, L.
Radic, Claudia Pamela
Rossetti, Liliana Carmen
Nemec, Diego Martín
de Brasi, Carlos Daniel
author Abelleyro, Miguel Martin
author_facet Abelleyro, Miguel Martin
Marchione, Vanina Daniela
Elhelou, L.
Radic, Claudia Pamela
Rossetti, Liliana Carmen
Nemec, Diego Martín
de Brasi, Carlos Daniel
author_role author
author2 Marchione, Vanina Daniela
Elhelou, L.
Radic, Claudia Pamela
Rossetti, Liliana Carmen
Nemec, Diego Martín
de Brasi, Carlos Daniel
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv F8
Hemophilia
Mosaicism
topic F8
Hemophilia
Mosaicism
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Large F8 deletions cause 10-15% of severe-Haemophilia A (HA) cases and associate with the highest clinical/biochemical severity and with significantly augmented risks for developing inhibitors against therapeutic FVIII. Only 45-50% of severe-HA cases present family history of the disease. In the remnant cases (sporadic-HA), the mutation origin defines different clinical scenarios in which the risk of recurrence and thus genetic counselling significantly vary. The origin of the causative mutation may be either pre-zygotic or post-zygotic generating a genetic mosaicism affecting, partially or totally, one or more tissue/organs including the gonads. Furthermore, the technical features of the genotyping approach for detecting and measuring an eventual genetic mosaicism critically affect its diagnosis. The quali-quantitative extent of somatic and germinal mosaicisms is passively assumed to be associated with the phenotypic expression of haemophilia severity and inheritance pattern, respectively. We present a case of a family affected with HA in which the clinical/biochemical severity and inheritance patterns associate with the observed fraction of mosaic cells bearing a F8-promoter deletion.
Fil: Abelleyro, Miguel Martin. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Marchione, Vanina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Elhelou, L.. Fundacion de la Hemofilia; Argentina
Fil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Rossetti, Liliana Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Nemec, Diego Martín. Fundacion de la Hemofilia; Argentina
Fil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires; Argentina
description Large F8 deletions cause 10-15% of severe-Haemophilia A (HA) cases and associate with the highest clinical/biochemical severity and with significantly augmented risks for developing inhibitors against therapeutic FVIII. Only 45-50% of severe-HA cases present family history of the disease. In the remnant cases (sporadic-HA), the mutation origin defines different clinical scenarios in which the risk of recurrence and thus genetic counselling significantly vary. The origin of the causative mutation may be either pre-zygotic or post-zygotic generating a genetic mosaicism affecting, partially or totally, one or more tissue/organs including the gonads. Furthermore, the technical features of the genotyping approach for detecting and measuring an eventual genetic mosaicism critically affect its diagnosis. The quali-quantitative extent of somatic and germinal mosaicisms is passively assumed to be associated with the phenotypic expression of haemophilia severity and inheritance pattern, respectively. We present a case of a family affected with HA in which the clinical/biochemical severity and inheritance patterns associate with the observed fraction of mosaic cells bearing a F8-promoter deletion.
publishDate 2018
dc.date.none.fl_str_mv 2018-03
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/11336/96383
Abelleyro, Miguel Martin; Marchione, Vanina Daniela; Elhelou, L.; Radic, Claudia Pamela; Rossetti, Liliana Carmen; et al.; Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation; Thieme Medical Publ Inc; Thrombosis and Haemostasis; 118; 3; 3-2018; 617-620
0340-6245
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96383
identifier_str_mv Abelleyro, Miguel Martin; Marchione, Vanina Daniela; Elhelou, L.; Radic, Claudia Pamela; Rossetti, Liliana Carmen; et al.; Somatic/Germinal Mosaicism of a F8 Promoter Deletion Confounds Clinical Predictions in a Family with Haemophilia A: Key Role of Genotype Quantitation; Thieme Medical Publ Inc; Thrombosis and Haemostasis; 118; 3; 3-2018; 617-620
0340-6245
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://europepmc.org/article/med/29534251
info:eu-repo/semantics/altIdentifier/doi/10.1055/s-0038-1623536
info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0038-1623536
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 Thieme Medical Publ Inc
publisher.none.fl_str_mv Thieme Medical Publ 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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