The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America

In this work, we review the clinical and genetic data in 14 Latin American propionic acidemia (PA) and 15 methylmalonic aciduria (MMAuria) patients. In the PA patients, we have identified four different changes in the PCCA gene, including one novel one (c.414+5G>A) affecting the splicing process....

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Autores principales: Pérez, Belén, Angaroni, Celia, Sánchez Alcudia, Rocio, Merinero, Begoña, Pérez Cerda, Celia, Specola, N., Rodríguez Pombo, P., Wajner, Moacir, De Kremer, Raquel, Cornejo, Verónica, Desviat, Lourdes R., Ugarte, Magdalena
Formato: Artículo PeerReviewed
Lenguaje:Español
Publicado: 2010
Materias:
QD Química
Acceso en línea:http://pa.bibdigital.ucc.edu.ar/5012/1/A_P%C3%A9rez.pdf
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Producción Académica Universidad Católica de Córdoba (UCCor) de Universidad Católica de Córdoba
id I38-R144-5012
record_format dspace
spelling I38-R144-50122025-11-10T17:15:47Z http://pa.bibdigital.ucc.edu.ar/5012/ The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America Pérez, Belén Angaroni, Celia Sánchez Alcudia, Rocio Merinero, Begoña Pérez Cerda, Celia Specola, N. Rodríguez Pombo, P. Wajner, Moacir De Kremer, Raquel Cornejo, Verónica Desviat, Lourdes R. Ugarte, Magdalena QD Química In this work, we review the clinical and genetic data in 14 Latin American propionic acidemia (PA) and 15 methylmalonic aciduria (MMAuria) patients. In the PA patients, we have identified four different changes in the PCCA gene, including one novel one (c.414+5G>A) affecting the splicing process. The PCCB mutational spectrum included two prevalent changes accounting for close to 60% of the mutant alleles studied and one novel change (c.494G>C) which by functional analysis is clearly pathogenic. We have also identified the deep intronic change c.654+462A>G, and the results of the antisense treatment in the patient's cell line confirmed the functional recovery of PCC activity. All PA patients bearing out-offrame mutations presented the disease earlier while patients bearing in hemizygous fashion p.E168K and p.R165W presented the disease later. Regarding the MMAuria patients, we have found three novel mutations in the MUT gene (c.1068G>A, c.1587-1594del8 and c.593delA) and one in the MMAB gene (c.349-1 G>C). Two patients with MMAuria with homocystinuria cblC type are carriers of the frequent c.271dupA mutation. All mut0, cblB and cblC patients presented the symptoms early and in general had more neurological complications, while cblA and mutpatients exhibited a late-onset presentation, and in general the long-term outcome was better. The results presented in this work emphasize the importance of the genetic analysis of the patients not only for diagnostic purposes but also to research into novel therapies based on the genotype. 2010-12-31 Artículo PeerReviewed application/pdf spa http://pa.bibdigital.ucc.edu.ar/5012/1/A_P%C3%A9rez.pdf Pérez, Belén, Angaroni, Celia, Sánchez Alcudia, Rocio, Merinero, Begoña, Pérez Cerda, Celia, Specola, N., Rodríguez Pombo, P., Wajner, Moacir, De Kremer, Raquel, Cornejo, Verónica, Desviat, Lourdes R. and Ugarte, Magdalena (2010) The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America. Journal of Inherited Metabolic Disease, 33. ISSN 01418955 info:eu-repo/semantics/altIdentifier/doi/10.1007/s10545-010-9116-4
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic QD Química
spellingShingle QD Química
Pérez, Belén
Angaroni, Celia
Sánchez Alcudia, Rocio
Merinero, Begoña
Pérez Cerda, Celia
Specola, N.
Rodríguez Pombo, P.
Wajner, Moacir
De Kremer, Raquel
Cornejo, Verónica
Desviat, Lourdes R.
Ugarte, Magdalena
The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America
topic_facet QD Química
description In this work, we review the clinical and genetic data in 14 Latin American propionic acidemia (PA) and 15 methylmalonic aciduria (MMAuria) patients. In the PA patients, we have identified four different changes in the PCCA gene, including one novel one (c.414+5G>A) affecting the splicing process. The PCCB mutational spectrum included two prevalent changes accounting for close to 60% of the mutant alleles studied and one novel change (c.494G>C) which by functional analysis is clearly pathogenic. We have also identified the deep intronic change c.654+462A>G, and the results of the antisense treatment in the patient's cell line confirmed the functional recovery of PCC activity. All PA patients bearing out-offrame mutations presented the disease earlier while patients bearing in hemizygous fashion p.E168K and p.R165W presented the disease later. Regarding the MMAuria patients, we have found three novel mutations in the MUT gene (c.1068G>A, c.1587-1594del8 and c.593delA) and one in the MMAB gene (c.349-1 G>C). Two patients with MMAuria with homocystinuria cblC type are carriers of the frequent c.271dupA mutation. All mut0, cblB and cblC patients presented the symptoms early and in general had more neurological complications, while cblA and mutpatients exhibited a late-onset presentation, and in general the long-term outcome was better. The results presented in this work emphasize the importance of the genetic analysis of the patients not only for diagnostic purposes but also to research into novel therapies based on the genotype.
format Artículo
PeerReviewed
author Pérez, Belén
Angaroni, Celia
Sánchez Alcudia, Rocio
Merinero, Begoña
Pérez Cerda, Celia
Specola, N.
Rodríguez Pombo, P.
Wajner, Moacir
De Kremer, Raquel
Cornejo, Verónica
Desviat, Lourdes R.
Ugarte, Magdalena
author_facet Pérez, Belén
Angaroni, Celia
Sánchez Alcudia, Rocio
Merinero, Begoña
Pérez Cerda, Celia
Specola, N.
Rodríguez Pombo, P.
Wajner, Moacir
De Kremer, Raquel
Cornejo, Verónica
Desviat, Lourdes R.
Ugarte, Magdalena
author_sort Pérez, Belén
title The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America
title_short The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America
title_full The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America
title_fullStr The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America
title_full_unstemmed The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin America
title_sort molecular landscape of propionic acidemia and methylmalonic aciduria in latin america
publishDate 2010
url http://pa.bibdigital.ucc.edu.ar/5012/1/A_P%C3%A9rez.pdf
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