A5067866696- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
- Genetic Neurodegenerative Diseases
- Metalloenzymes and iron-sulfur proteins
- Neurological diseases and metabolism
- RNA regulation and disease
- Fungal and yeast genetics research
- Biochemical Acid Research Studies
- DNA Repair Mechanisms
- Osteoarthritis Treatment and Mechanisms
- Porphyrin Metabolism and Disorders
- Musculoskeletal pain and rehabilitation
- Adipose Tissue and Metabolism
- Cardiomyopathy and Myosin Studies
- Coenzyme Q10 studies and effects
- Trace Elements in Health
- Peptidase Inhibition and Analysis
- Total Knee Arthroplasty Outcomes
- Ubiquitin and proteasome pathways
- Pain Management and Opioid Use
- Biomedical Research and Pathophysiology
- Obsessive-Compulsive Spectrum Disorders
University of Parma
2015-2025
Bambino Gesù Children's Hospital
2021
Amsterdam University Medical Centers
2021
Emma Kinderziekenhuis
2021
Amsterdam Neuroscience
2014
Cognitive Research (United States)
2014
<h3>Objectives:</h3> The study was focused on leukoencephalopathies of unknown cause in order to define a novel, homogeneous phenotype suggestive common genetic defect, based clinical and MRI findings, identify the causal defect shared by patients with this phenotype. <h3>Methods:</h3> Independent next-generation exome-sequencing studies were performed 2 unrelated leukoencephalopathy. findings these compared available MRIs database unclassified leukoencephalopathies; 11 similar abnormalities...
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...
Deficiencies in respiratory-chain complexes lead to a variety of clinical phenotypes resulting from inadequate energy production by the mitochondrial oxidative phosphorylation system. Defective expression mtDNA-encoded genes, caused mutations either or nuclear genome, represents rapidly growing group human disorders. By whole-exome sequencing, we identified two unrelated individuals carrying compound heterozygous variants TRMT5 (tRNA methyltransferase 5). encodes protein with strong homology...
By way of whole-exome sequencing, we identified a homozygous missense mutation in VARS2 one subject with microcephaly and epilepsy associated isolated deficiency the mitochondrial respiratory chain (MRC) complex I compound heterozygous mutations TARS2 two siblings presenting axial hypotonia severe psychomotor delay multiple MRC defects. The nucleotide variants segregated within families, were absent Single Nucleotide Polymorphism (SNP) databases are predicted to be deleterious. amount...
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,...
Defects in nuclear-encoded proteins of the mitochondrial translation machinery cause early-onset and tissue-specific deficiency one or more OXPHOS complexes. Here, we report a 7-year-old Italian boy with childhood-onset rapidly progressive encephalomyopathy stroke-like episodes. Multiple defects decreased mtDNA copy number (40%) were detected muscle homogenate. Clinical features combined low level plasma citrulline highly suggestive encephalopathy, lactic acidosis episodes (MELAS) syndrome,...
Mitochondrial dysfunction and altered proteostasis are central features of neurodegenerative diseases. The pitrilysin metallopeptidase 1 (PITRM1) is a mitochondrial matrix enzyme, which digests oligopeptides, including the targeting sequences that cleaved from proteins imported across inner membrane fraction amyloid beta (Aβ). We identified two siblings carrying homozygous PITRM1 missense mutation (c.548G>A, p.Arg183Gln) associated with an autosomal recessive, slowly progressive syndrome...
Abstract The possibility of using epigenetics in forensic investigation has gradually risen over the last few years. Epigenetic changes with their dynamic nature can either be inherited or accumulated throughout a lifetime and reversible, prompting use across various fields. In sciences, multiple applications have been proposed, such as discrimination monozygotic twins, identifying source biological trace left at crime scene, age prediction, determination body fluids tissues, human behavior...
A peculiar form of hepatocerebral mtDNA depletion syndrome is caused by mutations in the MPV17 gene, which encodes a small hydrophobic protein unknown function located mitochondrial inner membrane. In order to define molecular basis variants associated with human disorder, we have previously taken advantage S. cerevisiae as model system thanks presence an ortholog SYM1 . We demonstrate here that gene product essential maintain OXPHOS, glycogen storage, morphology and stability stressing...
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...
This study focused on the molecular characterization of patients with leukoencephalopathy associated a specific biochemical defect mitochondrial respiratory chain complex III, and explores impact distinct magnetic resonance imaging pattern to detect biallelic mutations in LYRM7 biochemically unclassified leukoencephalopathy. 'Targeted resequencing' custom panel including genes coding for proteins was performed III deficiency without genetic diagnosis.Based brain findings these patients, we...
<h3>Importance</h3> <i>YARS2</i>mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification new patients expands molecular spectrum mitochondrial disorders. <h3>Objectives</h3> To review clinical, molecular, genetic features of<i>YARS2</i>-related disease to demonstrate Scottish founder variant. <h3>Design, Setting, Participants</h3> An observational case series study was...
The human POLG gene encodes the catalytic subunit of mitochondrial DNA polymerase γ (pol γ). Mutations in pol are associated with a spectrum disease phenotypes including autosomal dominant and recessive forms progressive external ophthalmoplegia, spino-cerebellar ataxia epilepsy, Alpers–Huttenlocher hepatocerebral poliodystrophy. Multiple deletions, or depletion mtDNA affected tissues, molecular hallmarks mutations. To shed light on pathogenic mechanisms leading to these phenotypes, we have...
Abstract Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, the exception of glutaminyl mt-tRNA (mt-tRNA Gln ). is indirectly charged a transamidation reaction involving GatCAB amidotransferase complex. Defects machinery cause broad spectrum disorders, often fatal outcome. Here, we describe nine patients from five families genetic defects in complex subunit, including QRSL1 , GATB and GATC each showing lethal...
Abstract Childhood obsessive-compulsive disorder (OCD) stems from a bunch of restricted and repetitive behaviors, which are part normal behavioral repertoire up to the age 7. The persistence compulsive-like behaviors after that is often associated with unique comorbidity patterns, age-at-onset dependent reflect different developmental stages. In particular, OCD synchronically co-occurs broad constellation neurodevelopmental disorders, whereas diachronically it related an increased risk major...
The BCS1L gene encodes a mitochondrial chaperone which inserts the Fe2S2 iron–sulfur Rieske protein into nascent electron transfer complex III. Variants in are associated with spectrum of disorders, ranging from mild to severe phenotypes. Björnstad syndrome, milder condition, is characterized by sensorineural hearing loss (SNHL) and pili torti. More disorders include Complex III Deficiency, leads neuromuscular metabolic dysfunctions multi-systemic issues Growth Retardation, Aminoaciduria,...
To gain a wider view of the pathways that regulate mitochondrial function, we combined effect heat stress on respiratory capacity with discovery potential genome-wide screen in Saccharomyces cerevisiae. We identified 105 new genes whose deletion impairs growth at 37°C by interfering processes such as transcriptional regulation, ubiquitination and cytosolic tRNA wobble uridine modification via 5-methoxycarbonylmethyl-2-thiouridine formation. The latter process, specifically required for...
Abstract Background Chronic postoperative pain after total knee replacement (TKR) is a major clinical problem. It still unclear if specific inflammatory mediators are associated with long‐term complications. The current exploratory study aimed to (1) evaluate multiplex of 5 years TKR surgery in patients different degrees intensities and (2) any association the markers intensity, cognitive functional outcomes. Methods Plasma samples were collected from 76 (43 females; 33 males) analysed for...
(The American Journal of Human Genetics 99, 860–876; October 6, 2016) In the originally published version this article, Cristina Dallabona’s first name was unfortunately misspelled. It appears correctly here and online. The authors regret error. Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease Loss DNA Copy NumberThompson et al.The GeneticsSeptember 29, 2016In BriefMutations encoding mitochondrial ADP/ATP carrier AAC1 are well-recognized causes...