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dc.contributor.author
Rossetti, Liliana Carmen
dc.contributor.author
Szurkalo, Irupé
dc.contributor.author
Radic, Claudia Pamela
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Abelleyro, Miguel Martin
dc.contributor.author
Primiani, Laura
dc.contributor.author
Neme, Daniela
dc.contributor.author
Miguel, Candela
dc.contributor.author
Pérez Bianco, Raúl
dc.contributor.author
De Tezanos Pinto, Miguel
dc.contributor.author
Larripa, Irene Beatriz
dc.contributor.author
de Brasi, Carlos Daniel
dc.date.available
2019-09-04T15:52:26Z
dc.date.issued
2013-07
dc.identifier.citation
Rossetti, Liliana Carmen; Szurkalo, Irupé; Radic, Claudia Pamela; Abelleyro, Miguel Martin; Primiani, Laura; et al.; Factor VIII genotype characterization of haemophilia A affected patients with transient and permanent inhibitors: A comprehensive Argentine study of inhibitor risks; Wiley Blackwell Publishing, Inc; Haemophilia The Official Journal Of The World Federation Of Hemophilia; 19; 4; 7-2013; 511-518
dc.identifier.issn
1351-8216
dc.identifier.uri
http://hdl.handle.net/11336/82875
dc.description.abstract
Inhibitor development against exogenous factor VIII is a severe impairment of replacement therapy affecting 18% of Argentine patients with severe haemophilia A (HA). To study the molecular predisposition for inhibitor development, we genotyped 260 HA patients with and without inhibitors, countrywide. The inhibitor-positive population (19 transients, 15 low responders, LR and 70 high responders, HR) of 104 severe-HA patients showed 59 Inv22 (intron 22 inversions), 18 small ins/del-frameshifts, 12 gross deletions, 12 nonsense, one splicing defect and two missense, p.Arg531Pro and p.Leu575Pro, both LR and thought to impair FVIII A2 domain secondary structure. In addition, a patient with mild HA and HR showed the missense p.Glu1704Lys associated with two neutral intronic substitutions potentially affecting the A3 domain. A case/control study (84/143) permitted estimation of F8 genotype-specific inhibitor risks [OR; prevalence (CI)] in severe-HA patients classifying a high-risk group including multi-exon deletions [3.66; 55% (19-100)], Inv22 [1.8; 24% (19-100)] and nonsense in FVIII-LCh [1.2; 21% (7-59)]; an average risk group including single-exon deletions, indel frameshifts and nonsense-HCh; and a low-risk group represented by missense defects [0.14; 3% (0.6-11)]. Analysis of inhibitor concordance/discordance in related patients indicated additional genetic factors other than F8 genotype for inhibitor formation. No significant inhibitor-predisposing factors related to FVIII product exposure were found in age- and F8 genotype-stratified populations of severe-HA patients. In conclusion, the Argentine HA patient series presents similar global and mutation-specific inhibitor risks than the HA database and other published series. This case-specific information will help in designing fitted therapies and follow-up protocols in Argentina.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley Blackwell Publishing, Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
F8
dc.subject
Fviii Inhibitors
dc.subject
Hema
dc.subject
Mutation Characterization
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Factor VIII genotype characterization of haemophilia A affected patients with transient and permanent inhibitors: A comprehensive Argentine study of inhibitor risks
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-06-26T13:32:35Z
dc.journal.volume
19
dc.journal.number
4
dc.journal.pagination
511-518
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
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
dc.description.fil
Fil: Szurkalo, Irupé. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
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
dc.description.fil
Fil: Abelleyro, Miguel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: Primiani, Laura. Fundación de la Hemofilia Dr. Alfredo Pavlovsky; Argentina
dc.description.fil
Fil: Neme, Daniela. Fundación de la Hemofilia Dr. Alfredo Pavlovsky; Argentina
dc.description.fil
Fil: Miguel, Candela. Academia Nacional de Medicina de Buenos Aires; Argentina
dc.description.fil
Fil: Pérez Bianco, Raúl. Academia Nacional de Medicina de Buenos Aires; Argentina
dc.description.fil
Fil: De Tezanos Pinto, Miguel. Academia Nacional de Medicina de Buenos Aires; Argentina
dc.description.fil
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.description.fil
Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
dc.journal.title
Haemophilia The Official Journal Of The World Federation Of Hemophilia
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/hae.12105
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1111/hae.12105
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