Belén Pérez

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We describe the use of antisense morpholino oligonucleotides (AMOs) to restore normal splicing caused by intronic molecular defects identified in methylmalonic acidemia (MMA) and propionic acidemia (PA). The three new point mutations described in deep intronic regions increase the splicing scores of pseudoexons or generate consensus binding motifs for(More)
Propionic acidemia is an inherited metabolic disease caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC), one of the four biotin-dependent enzymes. PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause(More)
Propionic acidemia (PA) is a recessive disorder caused by a deficiency of propionyl-CoA carboxylase (PCC), a dodecameric enzyme composed of two different proteins alpha-PCC and beta-PCC, nuclear encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause PA and to date, up to 47 different allelic variations in the PCCB gene have been(More)
Propionic acidaemia (PA) is an autosomal recessive disorder caused by mutations in either of the PCCA or PCCB genes which encode the alpha and beta subunits, respectively, of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). In this work we have examined the biochemical findings and clinical outcome of 37 Spanish PA patients in relation to the(More)
Tetrahydrobiopterin (BH4) responsiveness in patients with mutations in the phenylalanine hydroxylase (PAH) gene is a recently recognized subtype of hyperphenylalaninemia characterized by a positive BH4 loading test. According to recent estimates, this phenotype may be quite common, suggesting that a large group of individuals may benefit from BH4(More)
The aim of this study was to characterize the phenylketonuria (PKU) alleles in the Spanish population, by both identifying the causative mutations and analyzing the RFLP haplotypes and the VNTR and short-tandem-repeat alleles associated with the phenylalanine hydroxylase (PAH) gene. We have investigated 129 independent mutant chromosomes, using denaturing(More)
Phenylketonuria patients harboring a subset of phenylalanine hydroxylase (PAH) mutations have recently shown normalization of blood phenylalanine levels upon oral administration of the PAH cofactor tetrahydrobiopterin [(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4)]. Several hypotheses have been put forward to explain BH4 responsiveness, but the molecular(More)
A subtype of phenylalanine hydroxylase (PAH) deficiency that responds to cofactor (tetrahydrobiopterin, BH4) supplementation has been associated with phenylketonuria (PKU) mutations. The underlying molecular mechanism of this responsiveness is as yet unknown and requires a detailed in vitro expression analysis of the associated mutations. With this aim, we(More)
Phenylketonuria is an autosomal recessive human genetic disease caused by mutations in the phenylalanine hydroxylase (PAH) gene. In the present work we have used different expression systems to reveal folding defects of the PAH protein caused by phenylketonuria mutations L348V, S349L, and V388M. The amount of mutant proteins and/or the residual activity can(More)
We present an extensive study of the genetic diversity of phenylalanine hydroxylase deficiency in the Spanish phenylketonuria population. We have analysed 195 PKU patients by DGGE analysis identifying 67 different mutations which represent 89% of the total mutant chromosomes. Seventeen mutations first described in Spain have not yet been detected elsewhere;(More)