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

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 depen...

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Autores principales: Silvera Ruíz, Silene Maite, Arranz Amo, Antonio, Dodelson de Kremer, Raquel, Larovere, Laura Elena
Formato: conferenceObject
Lenguaje:Inglés
Publicado: 2022
Materias:
Hiperammonemia
Ornithine
Acceso en línea:http://hdl.handle.net/11086/29954
Aporte de:
Repositorio Digital Universitario (UNC) de Universidad Nacional de Córdoba
id I10-R141-11086-29954
record_format dspace
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-141
collection Repositorio Digital Universitario (UNC)
language Inglés
topic Hiperammonemia
Ornithine
spellingShingle Hiperammonemia
Ornithine
Silvera Ruíz, Silene Maite
Arranz Amo, Antonio
Dodelson de Kremer, Raquel
Larovere, Laura Elena
Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
topic_facet Hiperammonemia
Ornithine
description 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.
format conferenceObject
author Silvera Ruíz, Silene Maite
Arranz Amo, Antonio
Dodelson de Kremer, Raquel
Larovere, Laura Elena
author_facet Silvera Ruíz, Silene Maite
Arranz Amo, Antonio
Dodelson de Kremer, Raquel
Larovere, Laura Elena
author_sort Silvera Ruíz, Silene Maite
title Ornithine transcarbamylase deficiency: identification of mutations, computational validation, and phenotypic correlation in argentinian patients
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
publishDate 2022
url http://hdl.handle.net/11086/29954
work_keys_str_mv AT silveraruizsilenemaite ornithinetranscarbamylasedeficiencyidentificationofmutationscomputationalvalidationandphenotypiccorrelationinargentinianpatients
AT arranzamoantonio ornithinetranscarbamylasedeficiencyidentificationofmutationscomputationalvalidationandphenotypiccorrelationinargentinianpatients
AT dodelsondekremerraquel ornithinetranscarbamylasedeficiencyidentificationofmutationscomputationalvalidationandphenotypiccorrelationinargentinianpatients
AT laroverelauraelena ornithinetranscarbamylasedeficiencyidentificationofmutationscomputationalvalidationandphenotypiccorrelationinargentinianpatients
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