Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients

Autores
Silvera Ruíz, Silene Maite; Arranz Amo, Antonio; Dodelson de Kremer, Raquel; Larovere, Laura Elena
Año de publicación
2013
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Fil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.
Fil: Silvera Ruíz, Silene Maite. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Silvera Ruíz, Silene Maite. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Ornithine transcarbamylase deficiency (OTCD; Online Mendelian Inheritance in Man [OMIM] 311250) is an urea cycle defect with Xlinked inheritance. In hemizygous males, neonatal or late onset depends on the degree of residual enzymatic activity. In heterozygous females, symptom presentation depends on Xchromosome inactivation. Mutation identification in OTC gene allows diagnostic confirmation and carrier detection. Objective: To identify mutations causing OTCD in Argentinian patients, to validate those changes, and to correlate them with phenotype. Methods: A total of 11 patients belonging to 8 families, 6 male patients, 2 with severe presentation and death during the neonatal period and 4 with late-onset (0.5-10 years) and 5 symptomatic women (0.8 to 4 years), 3 of them died and were diagnosed with OTCD. Molecular analysis of OTC gene was performed by polymerase chain reaction/multiplex ligation-dependent probe amplification/ Single-strand conformation polymorphism analysis and/ or sequencing, and missense changes validation was made using computational methods, PolyPhen, SIFT, and PopMusic 2.0. Results: We identified mutations in all patients; 2 were not previously described: 1 of splicing (c.540þ1G>A) and a deletion (delExon 2-10) and 6 were already reported: 1 of splicing (c.216þ1G>A) and 5 missense (p.Arg129His, p.Leu151Arg, p.Thr178Met, p.Ala208Thr, and p.Arg277Trp). Result validation was consistent with the applied computational programs and the patients presentation form. Conclusion: This analysis provides a better understanding of alterations responsible for the phenotypic expression. This work expands carrier detection capability allowing appropriate genetic counseling. Early detection of patients with OTCD is essential to reduce morbidity and mortality in affected individuals.
http://iem.sagepub.com/content/1/2326409813511871
Fil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.
Fil: Silvera Ruíz, Silene Maite. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Silvera Ruíz, Silene Maite. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Otras Ciencias de la Salud
Materia
Hiperammonemia
Ornithine
Nivel de accesibilidad
acceso abierto
Condiciones de uso
Repositorio
Repositorio Digital Universitario (UNC)
Institución
Universidad Nacional de Córdoba
OAI Identificador
oai:rdu.unc.edu.ar:11086/29954
Acceder
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oai_identifier_str oai:rdu.unc.edu.ar:11086/29954
network_acronym_str RDUUNC
repository_id_str 2572
network_name_str Repositorio Digital Universitario (UNC)
spelling Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patientsSilvera Ruíz, Silene MaiteArranz Amo, AntonioDodelson de Kremer, RaquelLarovere, Laura ElenaHiperammonemiaOrnithineFil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.Fil: Silvera Ruíz, Silene Maite. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Silvera Ruíz, Silene Maite. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Dodelson de Kremer, Raquel. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Larovere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Larovere, Laura Elena. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Ornithine transcarbamylase deficiency (OTCD; Online Mendelian Inheritance in Man [OMIM] 311250) is an urea cycle defect with Xlinked inheritance. In hemizygous males, neonatal or late onset depends on the degree of residual enzymatic activity. In heterozygous females, symptom presentation depends on Xchromosome inactivation. Mutation identification in OTC gene allows diagnostic confirmation and carrier detection. Objective: To identify mutations causing OTCD in Argentinian patients, to validate those changes, and to correlate them with phenotype. Methods: A total of 11 patients belonging to 8 families, 6 male patients, 2 with severe presentation and death during the neonatal period and 4 with late-onset (0.5-10 years) and 5 symptomatic women (0.8 to 4 years), 3 of them died and were diagnosed with OTCD. Molecular analysis of OTC gene was performed by polymerase chain reaction/multiplex ligation-dependent probe amplification/ Single-strand conformation polymorphism analysis and/ or sequencing, and missense changes validation was made using computational methods, PolyPhen, SIFT, and PopMusic 2.0. Results: We identified mutations in all patients; 2 were not previously described: 1 of splicing (c.540þ1G>A) and a deletion (delExon 2-10) and 6 were already reported: 1 of splicing (c.216þ1G>A) and 5 missense (p.Arg129His, p.Leu151Arg, p.Thr178Met, p.Ala208Thr, and p.Arg277Trp). Result validation was consistent with the applied computational programs and the patients presentation form. Conclusion: This analysis provides a better understanding of alterations responsible for the phenotypic expression. This work expands carrier detection capability allowing appropriate genetic counseling. Early detection of patients with OTCD is essential to reduce morbidity and mortality in affected individuals.http://iem.sagepub.com/content/1/2326409813511871Fil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.Fil: Silvera Ruíz, Silene Maite. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Silvera Ruíz, Silene Maite. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Dodelson de Kremer, Raquel. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Larovere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Fil: Larovere, Laura Elena. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.Otras Ciencias de la Salud2013info:eu-repo/semantics/conferenceObjectinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfhttp://hdl.handle.net/11086/29954enginfo:eu-repo/semantics/openAccessreponame:Repositorio Digital Universitario (UNC)instname:Universidad Nacional de Córdobainstacron:UNC2025-09-29T13:42:35Zoai:rdu.unc.edu.ar:11086/29954Institucionalhttps://rdu.unc.edu.ar/Universidad públicaNo correspondehttp://rdu.unc.edu.ar/oai/snrdoca.unc@gmail.comArgentinaNo correspondeNo correspondeNo correspondeopendoar:25722025-09-29 13:42:35.536Repositorio Digital Universitario (UNC) - Universidad Nacional de Córdobafalse
dc.title.none.fl_str_mv Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
title Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
spellingShingle Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
Silvera Ruíz, Silene Maite
Hiperammonemia
Ornithine
title_short Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
title_full Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
title_fullStr Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
title_full_unstemmed Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
title_sort Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
dc.creator.none.fl_str_mv Silvera Ruíz, Silene Maite
Arranz Amo, Antonio
Dodelson de Kremer, Raquel
Larovere, Laura Elena
author Silvera Ruíz, Silene Maite
author_facet Silvera Ruíz, Silene Maite
Arranz Amo, Antonio
Dodelson de Kremer, Raquel
Larovere, Laura Elena
author_role author
author2 Arranz Amo, Antonio
Dodelson de Kremer, Raquel
Larovere, Laura Elena
author2_role author
author
author
dc.subject.none.fl_str_mv Hiperammonemia
Ornithine
topic Hiperammonemia
Ornithine
dc.description.none.fl_txt_mv Fil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.
Fil: Silvera Ruíz, Silene Maite. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Silvera Ruíz, Silene Maite. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Ornithine transcarbamylase deficiency (OTCD; Online Mendelian Inheritance in Man [OMIM] 311250) is an urea cycle defect with Xlinked inheritance. In hemizygous males, neonatal or late onset depends on the degree of residual enzymatic activity. In heterozygous females, symptom presentation depends on Xchromosome inactivation. Mutation identification in OTC gene allows diagnostic confirmation and carrier detection. Objective: To identify mutations causing OTCD in Argentinian patients, to validate those changes, and to correlate them with phenotype. Methods: A total of 11 patients belonging to 8 families, 6 male patients, 2 with severe presentation and death during the neonatal period and 4 with late-onset (0.5-10 years) and 5 symptomatic women (0.8 to 4 years), 3 of them died and were diagnosed with OTCD. Molecular analysis of OTC gene was performed by polymerase chain reaction/multiplex ligation-dependent probe amplification/ Single-strand conformation polymorphism analysis and/ or sequencing, and missense changes validation was made using computational methods, PolyPhen, SIFT, and PopMusic 2.0. Results: We identified mutations in all patients; 2 were not previously described: 1 of splicing (c.540þ1G>A) and a deletion (delExon 2-10) and 6 were already reported: 1 of splicing (c.216þ1G>A) and 5 missense (p.Arg129His, p.Leu151Arg, p.Thr178Met, p.Ala208Thr, and p.Arg277Trp). Result validation was consistent with the applied computational programs and the patients presentation form. Conclusion: This analysis provides a better understanding of alterations responsible for the phenotypic expression. This work expands carrier detection capability allowing appropriate genetic counseling. Early detection of patients with OTCD is essential to reduce morbidity and mortality in affected individuals.
http://iem.sagepub.com/content/1/2326409813511871
Fil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.
Fil: Silvera Ruíz, Silene Maite. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Silvera Ruíz, Silene Maite. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Dodelson de Kremer, Raquel. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Fil: Larovere, Laura Elena. Ministerio de Salud de la Provincia de Córdoba. Hospital de Niños de la Santísima Trinidad. Centro de Estudio de las Metabolopatías Congénitas; Argentina.
Otras Ciencias de la Salud
description Fil: Arranz Amo, Antonio. Unitat de Metabolopaties. Hospital Univerisitari Materno Infanil; España.
publishDate 2013
dc.date.none.fl_str_mv 2013
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language eng
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