English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/139926
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Methylmalonic aciduria cblB type: Characterization of two novel mutations and mitochondrial dysfunction studies

AuthorsBrasil, Sandra ; Richard, Eva ; Jorge-Finnigan, A.; Leal, Fátima ; Merinero, Begoña ; Banerjee, R.; Desviat, Lourdes R. ; Ugarte, Magdalena ; Pérez, Belén
KeywordsMMAB gene
methylmalonic aciduria
mitochondrial function
Issue Date2015
PublisherBlackwell Publishing
CitationClinical Genetics 87: 576- 581 (2015)
Abstract© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Methylmalonic aciduria (MMA) cblB type is caused by mutations in the MMAB gene, which codes for the enzyme adenosine triphosphate (ATP): cobalamin adenosyltransferase (ATR). This study reports differences in the metabolic and disease outcomes of two pairs of siblings with MMA cblB type, respectively harbouring the novel changes p.His183Leu/p.Arg190dup (P1 and P2) and the previously described mutations p.Ile96Thr/p.Ser174fs (P3 and P4). Expression analysis showed p.His183Leu and p.Arg190dup to be destabilizing mutations. Both were associated with reduced ATR stability and a shorter half-life than wild-type ATR. Analysis of several parameters related to oxidative stress and mitochondrial function showed an increase in reactive oxygen species (ROS) content, a decrease in mitochondrial respiration and changes in mitochondria morphology and structure in patient-derived fibroblasts compared to control cells. The impairment in energy production and the presence of oxidative stress and fission of the mitochondrial reticulum suggested mitochondrial dysfunction in cblB patients' fibroblasts. The recovery of mitochondrial function should be a goal in efforts to improve the clinical outcome of MMA cblB type.
Identifiersdoi: 10.1111/cge.12426
issn: 1399-0004
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
PérezB_MethylmalonicAciduriaCBIB.pdf812,7 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.