A5037070650- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Genetics and Neurodevelopmental Disorders
- Neurological diseases and metabolism
- Lysosomal Storage Disorders Research
- Behavioral Health and Interventions
- Social and Intergroup Psychology
- RNA and protein synthesis mechanisms
- Media Influence and Health
- RNA regulation and disease
- Epilepsy research and treatment
- Glycogen Storage Diseases and Myoclonus
- Metalloenzymes and iron-sulfur proteins
- Biochemical and Molecular Research
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Neonatal Health and Biochemistry
- Folate and B Vitamins Research
- Hereditary Neurological Disorders
Fondazione IRCCS Istituto Neurologico Carlo Besta
2016-2025
John Wiley & Sons (United States)
2023
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2021
University of Catania
2015
Austin Health
2015
The University of Melbourne
2015
Fondazione Pierfranco e Luisa Mariani
2010
University of Geneva
1999-2007
University Children's Hospital Zurich
2003
Federico II University Hospital
2003
Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders progressive extrapyramidal signs neurological deterioration, characterized by in the basal ganglia. Exome sequencing revealed presence recessive missense mutations COASY, encoding coenzyme A (CoA) synthase one NBIA-affected subject. second unrelated individual carrying COASY was identified Sanger sequence analysis. CoA is bifunctional enzyme catalyzing final steps...
Dysfunction of mitochondrial respiration is an increasingly recognized cause isolated hypertrophic cardiomyopathy. To gain insight into the genetic origin this condition, we used next-generation exome sequencing to identify mutations in MTO1, which encodes translation optimization 1. Two affected siblings carried a maternal c.1858dup (p.Arg620Lysfs(∗)8) frameshift and paternal c.1282G>A (p.Ala428Thr) missense mutation. A third unrelated individual was homozygous for latter change. In both...
Dysregulation of RNA metabolism represents an important pathogenetic mechanism in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) due to the involvement DNA/RNA-binding proteins TDP-43 FUS and, more recently, C9ORF72. A potential link between dysregulation mitochondrial dysfunction is recently emerged disease models. To further investigate possible relationship these two mechanisms ALS/FTD, we studied mitochondria functionality human mutant TARDBP(p.A382T) C9ORF72...
Respiratory chain deficiencies exhibit a wide variety of clinical phenotypes resulting from defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mtDNA or nuclear genes coding for proteins. The underlying pathomechanisms affect numerous pathways involved physiology. By whole-exome and candidate gene sequencing, we identified 11 individuals 9 families carrying compound heterozygous homozygous GTPBP3, encoding...
Primary coenzyme Q10 (CoQ10) deficiencies are rare, clinically heterogeneous disorders caused by mutations in several genes encoding proteins involved CoQ10 biosynthesis. is an essential component of the electron transport chain (ETC), where it shuttles electrons from complex I or II to III. By whole-exome sequencing, we identified five individuals carrying biallelic COQ4. The precise function human COQ4 not known, but seems play a structural role stabilizing multiheteromeric that contains...
Isolated Complex I (CI) deficiency, the most frequent cause of mitochondrial disease, is a clinically and genetically heterogeneous condition. giant multiheteromeric enzyme composed seven ND subunits encoded by DNA (mtDNA) genes, at least 38 nuclear genes. To establish contribution to human encephalopathy versus gene mutations, we have been undertaking systematic analysis CI genes in cohort 46 adult paediatric patients with biochemically defined defect. Sequence entire mtDNA let us identify...
Given the complexity of respiratory chain structure, assembly and regulation, diagnostic workout for identification defects oxidative phosphorylation (OXPHOS) is a major challenge. Spectrophotometric assays, that measure activity individual complexes in tissue cell homogenates or isolated mitochondria, are highly specific, but their utilization limited by availability sufficient biological material intrinsic sensitivity. A further limitation specificity, which usually determines attenuation,...
<h3>Background</h3> Mitochondrial complex I deficiency is the most common cause of mitochondrial disease in childhood. Identification molecular basis difficult given clinical and genetic heterogeneity. Most patients lack a definition routine diagnostics. <h3>Methods</h3> A large-scale mutation screen 75 candidate genes 152 with was performed by high-resolution melting curve analysis Sanger sequencing. The causal role new allele confirmed functional complementation assays. phenotype carrying...
We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing the candidate gene MTO1, encoding mitochondrial-tRNA modifier 1, or whole exome analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth,...
Abstract Background Childhood‐onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood‐onset dystonia. Objective To define the frequency mutations in a cohort dystonic patients aged <18 years at onset, associated clinical and radiological phenotype, natural history disease. Methods Whole‐exome sequencing or customized gene panels were used to screen 65 who had previously tested negative for all other known...
153 secondary school students, all smokers, were either exposed to a strongly anti-smoking message originating from high status source (persuasive condition) or not (control condition). A questionnaire then measured set of variables concerning several aspects tobacco consumption (i.e., smoker identity, attitude, subjective norm, perceived lack behavioural control, smoking behaviour, and intention give up smoking). First, regression analysis shows that the smoker's identity plays direct...
Mutations in nuclear genes associated with defective complex III (cIII) of the mitochondrial respiratory chain are rare, having been found only two cIII assembly factors and, as private changes single families, three structural subunits. Recently, human LYRM7/MZM1L, ortholog yeast MZM1, has identified a new factor for cIII. In baby patient early onset, severe encephalopathy, lactic acidosis and profound, isolated deficiency skeletal muscle, we disease-segregating homozygous mutation...
Multiple Mitochondrial Dysfunction Syndrome (MMDS) comprises a group of severe autosomal recessive diseases with onset in early infancy and characterized by systemic disorder energy metabolism, resulting weakness, respiratory failure, lack neurological development, lactic acidosis death . Biochemical findings include defects complexes I, II III the mitochondrial chain deficiency Pyruvate dehydrogenase complex (PDHc). Three genes have been associated MMDS since now: NFU1, BOLA3, IBA 57. We...
Abstract Within the framework of an intergroup relations paradigm, three studies analysed role in‐group threat in discrimination and influence norms on discrimination. The first study showed that perceived socio‐economic underlies Swiss nationals' prejudice toward foreigners Switzerland. second third experimentally tested hypotheses, first, variations perception will produce change initial discrimination, and, second, norm (pro‐ vs. anti‐ discriminatory) is moderated by threat. In support...
<h3>Background:</h3> Ethylmalonic encephalopathy (EE) is a rare autosomal recessive metabolic disorder characterised by progressive encephalopathy, recurrent petechiae, acrocyanosis and chronic diarrhoea, with fatal outcome in early life. <h3>Methods:</h3> 14 patients EE were investigated for mutations the <i>ETHE1</i> gene. <h3>Results:</h3> Of patients, 5 found to carry novel mutations. <h3>Conclusions:</h3> This work expands our knowledge of causative EE.
To describe the clinical and neurophysiologic patterns of patients with neuronal ceroid lipofuscinoses associated CLN6 mutations.We reviewed features 11 different ages at onset.Clinical disease onset occurred within first decade life in 8 second third decades 3. All children presented progressive cognitive regression ataxia pyramidal extrapyramidal signs. Recurrent seizures, visual loss, myoclonus were mostly reported after a delay from onset; 7 chairbound had severe dementia less than 4...