Yolanda Campos

Yolanda Campos
Instituto de Salud Carlos III | ISCIII · UFIEC

40.73
 · 
PhD
About
144
Research items
4,503
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3,278
Citations
Research Experience
Jan 1990 - Oct 2007
Hospital Universitario 12 de Octubre
Position
  • Researcher
Jan 1989 - Sep 2007
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Research
Research items (144)
Preprint
Full-text available
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease affecting 1 in 350 people. The aim of Project MinE is to elucidate the pathophysiology of ALS through whole-genome sequencing at least 15,000 ALS patients and 7,500 controls at 30X coverage. Here, we present the Project MinE data browser (databrowser.projec...
Poster
The contribution of genetic and environmental factors to the pathogenesis of sporadic amyotrophic sclerosis (ALS) remains unclear. Genome sequencing has contributed to the acceleration in the discovery of genetic risk factors analyzing rare genetic variants or de novo mutations. To contribute to delineate the genetic architecture of the disease, we...
Article
Background: There is substantial interindividual variability in the rate and extent of CD4+ T cell recovery after starting combination antiretroviral therapy (cART). The aim of our study was to determine whether mitochondrial DNA (mtDNA) haplogroups are associated with recovery of CD4+ in HIV-infected patients on cART. Methods: We carried out a...
Article
: We performed a cross-sectional study in 469 HIV-infected patients, whose mitochondrial haplogroups were genotyped to study their association with the clinical pattern of AIDS progression. The chance of not having an AIDS progression was 1.45 [95% of confidence interval (CI) = 1.02 to 2.05, P = 0.035) times greater in patients with cluster HV and...
Article
We report, for the first time, a patient with an overlap MERRF-NARP syndrome who carries the mutation m.12300G>A in the mitochondrial tRNA(Leu(CUN)) gene. The mutation was heteroplamic and more abundant in her muscle and fibroblast than in blood from her oligosymptomatic mother. Single muscle fiber analysis revealed that the proportion of mutant mt...
Article
Mitochondrial DNA (mtDNA) haplogroups play an important role in susceptibility to metabolic disorders and cardiovascular disease. We carried out a cross-sectional study in 248 HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy to investigate whether mtDNA haplogroups had any influence on metabolic disorders. mtDNA gen...
Article
HIV infection, hepatitis C virus (HCV) liver disease, and mitochondrial DNA (mtDNA) polymorphisms are three possibly interrelated factors that might be associated with progression of liver disease. The aim of this study was to investigate whether mtDNA haplogroups had any influence on liver fibrosis progression in HIV/HCV coinfected patients. We ca...
Article
BACKGROUND:: Human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) liver disease and mitochondrial DNA (mtDNA) polymorphisms are three possibly interrelated factors that might be associated with progression of liver disease. The aim of this study was to investigate whether mtDNA haplogroups had any influence on liver fibrosis progre...
Article
Objectives - We analyzed the percentage of mitochondrial DNA (mtDNA) heteroplasmy in blood samples of 13 individuals belonging to a three family generation of myoclonic epilepsy with ragged-red fibers (MERRF) and compared the 5 affected patients and the 8 unaffected relatives. Material and methods - DNA was extracted from blood and muscle of the pr...
Article
We report an infant with complex I deficiency of the mitochondrial respiratory chain whose most conspicuous symptom at presentation was an Ohtahara syndrome. Review of the literature suggest that association of these two conditions is extremely rare. Despite the few cases reported, in our view Ohtahara syndrome should be considered as one of the fo...
Article
It has recently been reported that mutations in MPV17 gene may be causative of mtDNA depletion syndrome (MDS). Patients with this alteration presented with severe liver failure, hypoglycemia, growth retardation and neurological symptoms during the first year of life. We report on the clinical, biochemical and molecular findings of a patient present...
Article
Full-text available
Mutations in OPA1, a dynamin-related GTPase involved in mitochondrial fusion, cristae organization and control of apoptosis, have been linked to non-syndromic optic neuropathy transmitted as an autosomal-dominant trait (DOA). We here report on eight patients from six independent families showing that mutations in the OPA1 gene can also be responsib...
Article
Autosomal dominant PEO is associated with mutations in a number of nuclear genes affecting the intergenomic communication with mitochondrial DNA. We report a Spanish family showing a mild phenotype characterized by autosomal dominant ocular myopathy and morphological signs of mitochondrial dysfunction, that harboured a novel c.1071G>C (p.R357P) mut...
Article
We identified a novel G3283A transition in the mitochondrial DNA tRNA(Leu (UUR)) gene in a patient with ptosis, ophthalmoparesis and hyporeflexia. Muscle biopsy showed cytochrome oxidase positive ragged-red fibers, and defects of complexes I, III and IV of the mitochondrial respiratory chain. The mutation was heteroplasmic in muscle of the proband,...
Article
Mitochondrial DNA depletion (mtDNA) is an highly heterogeneous condition characterized by a decreased number of mtDNA copies. The patient is a 22-month-old girl with generalized hypotonia, marked weakness, respiratory failure, arterial hypertension, hyperlactacidemia, hepatosplenomegaly and mild hypertransaminasemia without hepatic failure neither...
Article
The 8993 T>G mutation in mitochondrial DNA has been associated with variable syndromes of differing severity ranging from maternally inherited Leigh's syndrome (MILS) to neuropathy, ataxia, retinitis pigmentosa (NARP), depending on the mutation loads in affected patients. We report a kindred with several members in the same generation suffering NAR...
Article
Our knowledge of mitochondrial respiratory chain diseases has increased dramatically in recent years, but relatively little information is available about their prevalence and incidence, either in pediatric or adult patients. This study reports incidence and prevalence estimates, and summarizes the clinical, biochemical, histologic, and genetic cha...
Article
Both dominant and recessive mutations were reported in the gene encoding the mitochondrial (mt) DNA polymerase gamma (POLG) in patients with progressive external ophthalmoplegia (PEO). Phenotypes other than PEO were recently documented in patients with mutations in the POLG gene. To screen patients with mitochondrial disease and multiple mtDNA dele...
Article
We studied a patient with the cardinal features of mitochondrial gastrointestinal encephalomyopathy (MNGIE). Two of his siblings showed a similar clinical picture. Muscle histochemistry displayed ragged red fibres (RRF) which were COX negative and biochemistry revealed combined defects of complexes III and IV of the mitochondrial respiratory chain....
Article
Clinical, electrophysiological, genetic and biochemical deficiencies variability were evaluated in 52 patients diagnosed of mitochondrial respiratory chain diseases (MRCD). 26 men and 26 women, aged 19 to 79 years, were tested by clinical examination, electrophysiological techniques, muscle biopsy and genetic and biochemical studies. The patients w...
Article
We studied renal involvement in 42 children with mitochondrial diseases (MDs). The diagnosis of MD was established by morphological, biochemical, and molecular genetic criteria. Renal disease was considered when patients had renal failure, nephrotic syndrome, Fanconi's syndrome or any symptomatic renal alteration. Mild tubular disorder was establis...
Article
Patients with mitochondrial myopathies (MM) usually suffer from exercise intolerance due to their impaired oxidative capacity and physical deconditioning. We evaluated the effects of a 12-week supervised randomized rehabilitation program involving endurance training in patients with MM. Twenty MM patients were assigned to a training or control grou...
Article
Full-text available
Mutations in mtDNA are responsible for a variety of mitochondrial diseases, where the mitochondrial tRNALeu(UUR) gene has especially hot spots for pathogenic mutations. Clinical features often depend on the tRNA species and/or positions of the mutations; however, molecular pathogenesis elucidating the relation between the location of the mutations...
Article
Full-text available
Two mutations (G8363A and A8296G) in the mtDNA (mitochondrial DNA) tRNA(Lys) gene have been associated with severe mitochondrial diseases in a number of reports. Their functional significance, however, remains unknown. We have already shown that homoplasmic cybrids harbouring the A8296G mutation display normal oxidative phosphorylation, although th...
Article
Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families. To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene. Using molecular genetic ap...
Article
Full-text available
Mitochondrial dysfunction might play a role in the pathogenesis of liver damage in erythropoietic protoporphyria (EPP). Changes in mitochondrial respiratory chain activities were evaluated in the Fechm1pas/Fechm1pas mouse model for EPP. Mice from different strains congenic for the same ferrochelatase germline mutation manifest variable degrees of h...
Article
West's syndrome is known to have symptomatic, cryptogenetic and idiopathic forms. Greater knowledge of the different pathologies and the development of new diagnostic techniques have allowed the list of symptomatic forms to be extended and congenital disorders of the metabolism account for a significant percentage as an aetiopathogenic factor. Yet,...
Article
Mitochondrial encephalomyopathies encompass a group of disorders that have impaired oxidative metabolism in skeletal muscles and central nervous system. Many compounds have been used in clinical trials on mitochondrial diseases, but the outcomes have been variable. It remains controversial whether treatment of mitochondrial diseases with coenzyme Q...
Article
Conventional EMG, nerve conduction studies and SFEMG were performed in 18 patients with various phenotypes of MD. 14 cases showed findings consistent with mild myopathy, 2 patients signs of sensory-motor axonal neuropathy and 2 cases a mixture of myopathy and axonal neuropathy. Motor unit fiber density was mild increased in 8 out of 13 tested cases...
Article
We report 50 patients with various clinical phenotypes of mitochondrial disease studied over the past 10 years in a large urban area (Madrid Health Area 5). The clinical phenotypes showed a large variety of abnormalities in molecular biology and biochemistry. The prevalence of mitochondrial diseases was found to be 5.7 per 100,000 in the population...
Article
We studied two patients with ragged-red fibers and combined defects of the mitochondrial respiratory chain in their muscle biopsy. One had mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and harbored a T3258C transition in the tRNA(Leu(UUR)) gene. The other showed myopathy plus cardiomyopathy and had an A3280G mutation i...
Article
Multiple symmetric lipomatosis (MSL), which is predominantly found in middle aged males, is characterised by accumulations of fat in the neck, shoulders and other parts of the trunk, and sometimes associated with different neurological manifestations, both central and peripheral. Although its aetiology is unknown, it has been described as associate...
Article
Myotonic dystrophy type 1 (DM1), an autosomal dominant disease characterized by a CTG expansion in the 3' region of the DMPK gene in chromosome 19, is a highly heterogeneous disease. In this study, we present a family with early onset-classical type DM, and a homogeneous phenotype highlighted by severe neuromuscular symptoms and mental dysfunction...
Article
Thirty-five mitochondrial (mt) DNAs from Spain that harbor the mutation A3243G in association with either MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) syndrome or a wide array of disease phenotypes (ranging from diabetes and deafness to a mixture of chronic progressive external ophthalmoplegic symptoms an...
Article
Sixteen unrelated Southern European patients with the mitochondrial depletion syndrome (MDS) were analyzed for mutations in the TK2 and DGUOK genes. Three novel mutations were identified in TK2 (R183G, R254X, and 142insG). When we analyzed additional genes involved in the dNTPs pool, such as SLC25A19 (DNC) and NT5M (d-NT2), we did not detect mutati...
Article
García-Velasco A, Gómez-Escalonilla C, Guerra-Vales JM, Cabello A, Campos Y, Arenas J (Universitary Hospital 12 de Octubre, Madrid, Spain). Intestinal pseudo-obstruction and urinary retention: cardinal features of a mitochondrial DNA-related disease (Case report). J Intern Med 2003; 253: 381–385. The syndrome of mitochondrial myopathy, encephalopat...
Article
The authors describe a patient who presented with myoglobinuria after starting cerivastatin-gemfibrozil therapy. Muscle histochemistry revealed ragged-red fibers and cytochrome c oxidase negative (COX) fibers, and biochemistry showed a defect of COX activity. Immunoblot analysis showed a 60% reduction of COX I and COX II polypeptides. Cerivastatin...
Article
We performed a genetic analysis of the Cu/Zn superoxide dismutase gene (SOD1) in Spanish patients with sporadic or familial amyotrophic lateral sclerosis (ALS). We found mutations in 2 of 11 families (18%) with ALS. In addition, 1 of the 87 sporadic ALS patients studied harbored a mutation in the same gene. We identified G37R in exon 2 of the SOD1...
Article
Mitochondria have a key role in cell metabolism, being the major site of ATP production via oxidative phosphorylation. This system consists of five multiprotein complexes, whose individuals subunits are encoded either by the mitochondrial or by the nuclear genome. Respiratory chain enzyme deficiencies result in devastating, usually multisystem, dis...
Article
Transmitochondrial cybrid cell lines homoplasmic for the A8296G mtDNA transition, a mutation associated with several mitochondrial diseases, have a normal oxidative phosphorylation function, as shown by oxygen consumption, lactate production, respiratory enzyme activities, and growth using galactose as the only source of energy. The synthesis of mi...
Article
We report a patient with progressive external ophthalmoplegia (PEO), exercise intolerance, and deafness after aminoglycoside exposure, harboring two pathogenic mutations in her mtDNA: an A1555G in the 12S rRNA gene and a G4309A in the tRNA(Ile) gene. Muscle histochemistry showed abundant ragged-red fibers, and biochemistry revealed normal respirato...
Article
We report a patient with progressive external ophthalmoplegia (PEO), exercise intolerance, and deafness after aminoglycoside exposure, harboring two pathogenic mutations in her mtDNA: an A1555G in the 12S rRNA gene and a G4309A in the tRNAIle gene. Muscle histochemistry showed abundant ragged-red fibers, and biochemistry revealed normal respiratory...
Chapter
Defects of substrate utilisation in muscle cause two main clinical presentations. One is characterized by acute, recurrent, reversible muscle dysfunction, manifesting as exercise intolerance or myalgia, and often leading to episodes of rhabdomyolisis and myoglobinuria. The second presentation is characterized by fixed, often progressive weakness, s...
Article
We report the case of a fetus aborted at gestation week 20 because of hydranencephalic-hydrocephalic syndrome. The fetus was the third pregnancy of a nonconsanguineous couple whose first child exhibited congenital hydranencephalic-hydrocephalic syndrome associated with muscle histology findings consistent with mitochondrial cytopathy and deficiency...
Article
We studied a 57-year-old female patient with clinical and biochemical evidences of McArdle's disease. Her muscle biopsy also revealed signs of mitochondrial proliferation, scattered RRF, and a deficit in complex I of the respiratory chain. Molecular genetic analysis showed that the patient was heterozygous for the most common mutation at codon 49 i...
Article
It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. Patients aged </=50 years, admitted to the Stroke Unit from January 1...
Article
Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. To characterize a...
Article
Full-text available
We report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.8% of patients and 9% of mutant alleles. The W797R mutation was observed in 16.5% of patients, acco...
Article
We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-posit...
Article
We studied a patient with ptosis, ophthalmoparesis, and exercise intolerance who showed in her muscle biopsy ragged-red fibers and combined defects of the complexes I and IV of the mitochondrial respiratory chain. Molecular analysis revealed a T3273C transition in the mitochondrial DNA tRNA(Leu(UUR)) gene. The mutation was heteroplasmic and very ab...
Article
MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes) is a mitochondrial disease related to the mitochondrial DNA mutation. The tRNALeu(UUR) mutation at the base pair 3234 is associated to 80% of cases of MELAS syndrome. The onset with the stroke like episodes is often before the age 40. Herpes simplex e...
Article
Multiple symmetrical lipomatosis (LSM) is characterized by the development of symmetrical lipomas and is often associated with axonal polyneuropathy (PNP). Presentation is usually sporadic. Familial cases have been reported infrequently, with variable modes of inheritance. The pathogenesis is unknown. It has been related to mitochondrial cytopathy...
Article
We report two siblings with McArdle's disease who are both compound heterozygotes for two non-identical frameshift mutations in the PYGM gene; a previously reported 753 delA in exon 18 and a novel 387 insA/del 8 bp in exon 10. The novel mutation is predicted to result in premature termination of translation 33 amino acids downstream of the site of...
Article
Las pruebas de ejercicio cardiopulmonar han sido utilizadas en el diagnóstico delas miopatías metabólicas. Se desconoce si existe un patrón de respuesta anormal en las miopatíasmitocondriales con afectación leve y la utilidad de esta técnica en el diagnóstico de sospechainicial.Pacientes y métodosEstudio prospectivo en 26 pacientes con miopatías mi...
Article
We studied myocardial tissue from 25 cardiac transplant recipients, who had end-stage congestive heart failure (CHF), and from 21 control donor hearts. Concentrations of total carnitine (TC), free carnitine (FC), short-chain acylcarnitines, long-chain acylcarnitines (LCAC) as well as carnitine palmitoyltransferase (CPT) activities were measured in...
Article
Isolated or combined enzyme deficiencies of the mitochondrial respiratory chain results in a number of clinical heterogeneous conditions. When presented in the neonatal period or early in the infancy the course is usually severe, although isolated cases with benign evolution have also been described. To describe the clinical and biochemical charact...
Article
We studied a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes who had morphologically and biochemically abnormal muscle mitochondria. Molecular analysis revealed a T8316C transition in the mitochondrial DNA tRNA(Lys) gene. The mutation was homoplasmic in muscle from the proposita, heteroplasmic in her blood, a...
Article
We found six patients with AMPD deficiency in muscle who were homozygous for the most common mutation, Q12X in the AMPD gene (AMPD1), associated with this disease. Three patients had AMPD deficiency alone, showing a mild clinical phenotype. Two patients showed a defect of PPL in muscle, and were homozygous for the most common mutation associated wi...
Article
We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous C-to-A mutation results in the replacement of a highly conserved alanine at amino acid position 659 with an aspartic acid in the C-terminal domain of the myophosphorylase gene protein, near binding sites for pyrid...
Article
Objective: We carry out a review of the current basic genetic, biochemical, clinical, diagnostic and therapeutic aspects of mitochondrial cytopathies due to deficiencies in the mitochondrial respiratory chain complexes, which appear clinically during childhood and/or adolescence. Development: The clinical description has been divided into two gr...
Article
The mutation T3308C results in a Met --> Thr change at the highly conserved amino acid position 1 of the mtDNA ND1 gene (M1T). To study its potential pathogenic effect we have carried out a combination of mitochondrial protein synthesis and Northern and Western analyses. Our data demonstrate that M1T mutation does not affect the efficiency of the s...
Article
Carnitine palmitoyltransferase II (CPT II) deficiency is the most common recessively inherited disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. We studied 5 Spanish patients with CPT II deficiency from four unrelated families. Four patients had the typical clinical phenotype of muscle C...
Article
Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We...
Article
We report two novel homozygous mutations in the myophosphorylase gene (PYGM) in a patient with McArdle's disease. A C-to-T transition that changed an arginine to tryptophan at codon 193 (R193W) in exon 5, and a deletion of two adenine base pairs in exon 20 at codon 794/795 (794/795 delAA) were identified. Several lines of evidence suggest the patho...
Article
Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We...
Article
Exercise tests has been used in the diagnosis of metabolic myopathies. If there is an abnormal response pattern in mild mitochondrial myopathy (MM) and her role in the initial suspect diagnostic is unknown. Prospective study of 26 patients with mitochondrial myopathy (15 men, 11 women) and a control group of 14 sedentary volunteers (9 men, 5 woman)...
Article
A heterozygous C-to-A substitution at codon 487, changing a highly conserved threonine to an asparagine (T487N) was identified in two siblings with McArdle's disease who were also heterozygous for the nonsense mutation at codon 49 (R49X). Our data further expand the genetic heterogeneity in patients with McArdle's disease.
Article
We studied a 62 year-old woman with a clinical phenotype characterized by encephalopathy, restrictive cardiomyopathy, and prominent intestinal pseudo-obstruction. Muscle morphology showed ragged red fibres with ultrastructurally abnormal mitochondrial whereas muscle respiratory chain was normal. Molecular genetics revealed the 'common deletion' in...
Article
We identified a novel missense mutation in the myophosphorylase gene (PYGM) in a Spanish patient with McArdle's disease. This homozygous T-to-C transition results in the replacement of a highly conserved tryptophan at amino acid position (aa) 797 with an arginine in the C-terminal domain of the PYGM protein. The lack of enzyme activity in the proba...