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34 results on '"Perez-Cerda, C."'

4. Four Years’ Experience in the Diagnosis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency in Infants Detected in Three Spanish Newborn Screening Centers

Author

Merinero, B., Alcaide, P., Martín-Hernández, E., Morais, A., García-Silva, M. T., Quijada-Fraile, P., Pedrón-Giner, C., Dulin, E., Yahyaoui, R., Egea, J. M., Belanger-Quintana, A., Blasco-Alonso, J., Fernandez Ruano, M. L., Besga, B., Ferrer-López, I., Leal, F., Ugarte, M., Ruiz-Sala, P., Pérez, B., Pérez-Cerdá, C., Morava, Eva, editor, Baumgartner, Matthias, editor, Patterson, Marc, editor, Rahman, Shamima, editor, Zschocke, Johannes, editor, and Peters, Verena, editor

Published
2018
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12. Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy

Author

Izquierdo-Serra M, Martinez-Monseny T, Lopez L, Carrillo-Garcia J, Edo A, Ortigoza-Escobar JD, Garcia O, Cancho-Candela R, Carrasco-Marina ML, Gutierrez-Solana LG, Cuadras-Palleja D, Muchart-Lopez J, Montero-Sanchez R, Artuch-Iriberri R, Perez-Cerda C, Perez B, Pérez-Dueñas B, Macaya A, Fernandez-Fernandez JM, and Serrano M

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, CaV2.1 voltage-gated calcium channel, magentic resonance Imaging (MRI), cerebellum, stroke-like, ataxia, Ca(V)2, 1 voltage-gated calcium channel, congenital disorders of glycosylation
Abstract

Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding Ca(V)2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal Ca(V)2.1 function due to aberrant N-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients' group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show similarities. Hypoglycosylation of both Ca(V)2.1 subunits (a(1A) and a(2a)) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N-glycosylation site N283 at a(1A) contributes to a gain-of-function by lessening Ca(V)2.1 inactivation. Hypoglycosylation of the a2d subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the Ca(V)2.1 channel. Ca(V)2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant Ca(V)2.1 N-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities.

Published
2018

13. Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation

Author

Pena-Quintana, L., Scherer, G., Curbelo-Estevez, M. L., Jimenez-Acosta, F., Hartmann, B., La Roche, F., Meavilla-Olivas, S., Perez-Cerda, C., Garcia-Segarra, N., Giguere, Y., Huppke, P., Mitchell, G. A., Monch, E., Trump, D., Vianey-Saban, Christine, Trimble, E. R., Vitoria-Minana, I., Reyes-Suarez, D., Ramirez-Lorenzo, T., Tugores, A., Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, Richner-Hanhart, Adolescent, Genotype, FEATURES, [SDV]Life Sciences [q-bio], DIAGNOSIS, Polymorphism, Single Nucleotide, Young Adult, TAT GENE, RICHNER-HANHART-SYNDROME, Humans, OCULOCUTANEOUS TYROSINEMIA, genetics, Age of Onset, Child, Alleles, Genetic Association Studies, Tyrosine Transaminase, DELAYED, IDENTIFICATION, Tyrosinemias, DELETION, WILSON-DISEASE, Infant, Newborn, Infant, AMINOTRANSFERASE GENE, PLANTAR KERATODERMA, tyrosinemia, Founder Effect, Pedigree, Phenotype, Genetic Loci, Child, Preschool, Mutation, Female, TAT
Abstract

BACKGROUND: Tyrosinemia type II, also known as Richner-Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability. AIMS: To update disease-causing mutations and current clinical knowledge of the disease. MATERIALS AND METHODS: Genetic and clinical information were obtained from a collection of both unreported and previously reported cases. RESULTS: We report 106 families, represented by 143 individuals, carrying a total of 36 genetic variants, 11 of them not previously known to be associated with the disease. Variants include 3 large deletions, 21 non-synonymous and 5 nonsense amino-acid changes, 5 frameshifts and 2 splice variants. We also report 5 patients from Gran Canaria, representing the largest known group of unrelated families sharing the same P406L mutation. CONCLUSIONS: Data analysis did not reveal a genotype-phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns.

Published
2017

14. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation

Author

Jansen, J.C., Cirak, S., Scherpenzeel, M. van, Timal, S., Reunert, J., Rust, S., Perez, B., Vicogne, D., Krawitz, P., Wada, Y., Ashikov, A.M., Perez-Cerda, C., Medrano, C., Arnoldy, A., Hoischen, A., Huijben, K., Steenbergen, G., Quelhas, D., Diogo, L., Rymen, D., Jaeken, J., Guffon, N., Cheillan, D., Heuvel, B. van den, Maeda, Y., Kaiser, O., Schara, U., Gerner, P., Boogert, M.A. van den, Holleboom, A.G., Nassogne, M.C., Sokal, E., Salomon, J., Bogaart, G. van den, Drenth, J.P., Huynen, M.A., Veltman, J.A., Wevers, R.A., Morava, E., Matthijs, G., Foulquier, F., Marquardt, T., Lefeber, D.J., Jansen, J.C., Cirak, S., Scherpenzeel, M. van, Timal, S., Reunert, J., Rust, S., Perez, B., Vicogne, D., Krawitz, P., Wada, Y., Ashikov, A.M., Perez-Cerda, C., Medrano, C., Arnoldy, A., Hoischen, A., Huijben, K., Steenbergen, G., Quelhas, D., Diogo, L., Rymen, D., Jaeken, J., Guffon, N., Cheillan, D., Heuvel, B. van den, Maeda, Y., Kaiser, O., Schara, U., Gerner, P., Boogert, M.A. van den, Holleboom, A.G., Nassogne, M.C., Sokal, E., Salomon, J., Bogaart, G. van den, Drenth, J.P., Huynen, M.A., Veltman, J.A., Wevers, R.A., Morava, E., Matthijs, G., Foulquier, F., Marquardt, T., and Lefeber, D.J.

Abstract

Contains fulltext : 167630.pdf (publisher's version ) (Closed access), Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V-ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal glyc

Published
2016

19. Delayed onset holocarboxylase synthetase deficiency with normal pyruvate carboxylase activity

Author

Vitoria, I, Rausell, D, Gonzalez, I, Perez-Cerda, C, and Dalmau, J

Subjects
Holocarboxylase synthetase, Biotin, Multiple carboxylase deficiency
Abstract

We report a case of holocarboxylase synthetase deficiency with normal pyruvate carboxylase activity in the lymphocytes of an 8 year-old girl with clinical toxicity without the classic dermatological involvement. The identification of three nucleotide changes in the holocarboxylase synthetase (HLCS) gene, only one of them described as a pathogenic mutation could be related to a slight variant of the disease that would explain the unusual presentation beyond the age of infant. Treatment with biotin at 40 mg/day with protein controlled diet allows normal physical growth and psychomotor development for their age. (C) 2013 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L. All rights reserved.

Published
2014

27. Screening for adenylosuccinate lyase deficiency: Clinical, biochemical and molecular findings in four patients

Author

UCL - MD/BICL - Département de biochimie et de biologie cellulaire, Castro, M., Perez-Cerda, C, Merinero, B, Garcia, MJ, Bernar, J, Nagel, AG, Torres, J., Bermudez, M, Garavito, P, Marie, S., Vincent, F., Van den Berghe, Georges, Ugarte, M, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, Castro, M., Perez-Cerda, C, Merinero, B, Garcia, MJ, Bernar, J, Nagel, AG, Torres, J., Bermudez, M, Garavito, P, Marie, S., Vincent, F., Van den Berghe, Georges, and Ugarte, M

Abstract

Adenylosuccinate lyase deficiency is an autosomal recessive defect of purine metabolism. Succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr) are the disease marker metabolites in physiological fluids. The Bratton-Marshall test for detection of SAICAr in urine has been added to the selective screening for inborn errors of metabolism that is carried out in our lab. During the last three years, around 2000 patients have been screened by this method, resulting in the detection of four new cases with this disease. They all presented with severe psychomotor delay, hypotonia and refractory epilepsy since the neonatal period. The S-Ado/SAICAr ratio in cerebrospinal fluid was below 2, indicating that they correspond to the most severe form of the disease. New missense mutations were found in a heterozygous fashion in three patients. The study of purines in all patients with neurological disease of unknown etiology is highly recommended.

Published
2002

28. A nonsense mutation in exon 2 of the 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL) gene producing three mature mRNAs is the main cause of 3-hydroxy-3-methylglutaric aciduria in European Mediterranean patients

Author

Casale, C.H., Casals, N., Pie, J., Zapater, N., Perez-Cerda, C., Merinero, B., Martinez-Pardo, M., Garcia-Penas, J.J., Garcia-Gonzalez, J.M., Lama, R., Poll-The, B.T., Smeitink, J.A.M., Wanders, R.J., Ugarte, M., Hegardt, F.G., Casale, C.H., Casals, N., Pie, J., Zapater, N., Perez-Cerda, C., Merinero, B., Martinez-Pardo, M., Garcia-Penas, J.J., Garcia-Gonzalez, J.M., Lama, R., Poll-The, B.T., Smeitink, J.A.M., Wanders, R.J., Ugarte, M., and Hegardt, F.G.

Abstract

Item does not contain fulltext

Published
1998

30. Biotinidase deficiency: result of treatment with biotin from age 12 years

Author

Casado De Frias, E., Campos-Castello, J., Careaga Maldonado, J., and Perez Cerda, C.

Abstract

A boy with severe symptoms of biotinidase deficiency diagnosed at the age of 12 years showed a remarkable improvement of his neurological picture and normalization of brain magnetic resonance imaging abnormalities when prescribed oral biotin.

Published
1997
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31. 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease.

Author

Perez-Cerda C, García-Villoria J, Ofman R, Sala PR, Merinero B, Ramos J, García-Silva MT, Beseler B, Dalmau J, Wanders RJ, Ugarte M, and Ribes A

Subjects
3-Hydroxyacyl CoA Dehydrogenases, Alcohol Oxidoreductases deficiency, Amino Acid Metabolism, Inborn Errors enzymology, Child, Female, Humans, Infant, Infant, Newborn, Male, Mitochondrial Diseases enzymology, Alcohol Oxidoreductases genetics, Amino Acid Metabolism, Inborn Errors metabolism, Chromosomes, Human, X, Genetic Linkage, Isoleucine metabolism, Mitochondrial Diseases metabolism
Abstract

We describe three patients, from two Spanish families, with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, a recently described X-linked neurodegenerative inborn error of isoleucine metabolism. Two of them are males with severe lactic acidosis suggestive of a mitochondrial encephalopathy, and the third is a female who was less severely affected, suggesting skewed X-inactivation. Molecular studies revealed a new missense mutation, 740A-->G, in one family and a previously described mutation, 388C-->T, in the other, causing the amino acid substitutions N247S and R130C, respectively. Both male patients died, one of them despite treatment with an isoleucine-restricted diet, but the disease has remained stable in the female patient after 1 y of treatment.

Published
2005
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32. Characterization of six mutations in five Spanish patients with mitochondrial acetoacetyl-CoA thiolase deficiency: effects of amino acid substitutions on tertiary structure.

Author

Fukao T, Nakamura H, Nakamura K, Perez-Cerda C, Baldellou A, Barrionuevo CR, Castello FG, Kohno Y, Ugarte M, and Kondo N

Subjects
Acetyl-CoA C-Acyltransferase chemistry, Acetyl-CoA C-Acyltransferase genetics, Amino Acid Sequence, Amino Acid Substitution, DNA chemistry, DNA genetics, DNA Mutational Analysis, DNA, Complementary chemistry, DNA, Complementary genetics, Enzyme Stability, Female, Humans, Immunoblotting, Infant, Metabolism, Inborn Errors enzymology, Models, Molecular, Molecular Sequence Data, Mutation, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Acetyl-CoA C-Acyltransferase deficiency, Metabolism, Inborn Errors genetics, Mitochondria enzymology
Abstract

Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inborn error of ketone body and isoleucine metabolism. We identified and characterized 6 mutations, DelE85, K124R, A127V, Q145E, G152A, and E345V in 5 Spanish T2-deficient patients. Transient expression of mutant cDNAs was done at 37 and at 30 degrees C. Expression of the Q145E mutant cDNA resulted in about 12.5% normal amount at 37 degrees C and it retained 15% residual T2, indicating that specific activity of Q145E mutant protein was almost normal. This mutation reduced the heat stability of T2 activity. Although no significant residual activity was detected in either the G152A and A127V substitution, mutant proteins were detected, at 12.5% the normal amount at 37 degrees C and one-half normal at 30 degrees C for A127V, and 25 % only at 30 degrees C for G152A. Mutant proteins with Q145E, G152A, or A127V accumulated at 30 degrees C expression were stable for 48 h at 37 degrees C after cycloheximide treatment. Expression of DelE85, K124R, and E345V cDNAs gave neither residual T2 protein nor T2 activity. We constructed an improved tertiary structural model of T2 based on the X-ray crystal structure of acetoacetyl-CoA thiolase of Zoogloea ramigera. On the basis of this model, K124, A127, and G152 are located near the active site, mutations of which might affect catalytic function whereas Q145E, De185E, and E345V are distant from the active site with mutants being expected to destabilize the tertiary structure, especially during protein folding and dimerization.

Published
2002
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33. A novel single-base substitution (380C>T) that activates a 5-base downstream cryptic splice-acceptor site within exon 5 in almost all transcripts in the human mitochondrial acetoacetyl-CoA thiolase gene.

Author

Nakamura K, Fukao T, Perez-Cerda C, Luque C, Song XQ, Naiki Y, Kohno Y, Ugarte M, and Kondo N

Subjects
Binding Sites, Cysteine chemistry, DNA Mutational Analysis, Exons, Female, Fibroblasts metabolism, Gene Deletion, Humans, Immunoblotting, Introns, Metabolism, Inborn Errors genetics, Models, Genetic, Mutation, RNA Splicing, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Acetyl-CoA C-Acyltransferase deficiency, Acetyl-CoA C-Acyltransferase genetics, Mitochondria enzymology, Point Mutation, RNA Splice Sites
Abstract

Most mutation-related aberrant splicing occurs in the conserved splice-acceptor and -donor sites and some exonic mutations also affect splicing. We identified and characterized a point mutation (380C>T) in a Spanish patient (GK25) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK25 is a homozygote of 380C>T, which activates a cryptic splice-acceptor site 5 bases downstream from 380C>T within exon 5, causing aberrant splicing in 94% of transcripts. The aberrant splicing results in a 17-amino acids deletion, including the active-site 126Cys. The 380C>T mutation also results in A127V mutation in 6% of transcripts. Transient expression analysis showed that the A127V mutation did not retain T2 activity, indicating that 380C>T was a null mutation. Although this cryptic splice site has a higher Shapiro and Senapathy's score (86) in even a normal sequence than the authentic splice-acceptor site of intron 4 (78), it is not used in normal controls. While the 380C>T mutation increases the score slightly (90), the cryptic splice site is used in almost all transcripts in GK25 fibroblasts. This is an example in which a point mutation activates a cryptic splice-acceptor site motif that is used preferentially over the upstream authentic splice site., (Copyright 2001 Academic Press.)

Published
2001
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