A5056579297- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Drug-Induced Ocular Toxicity
- Protein Tyrosine Phosphatases
- Glycogen Storage Diseases and Myoclonus
- Endoplasmic Reticulum Stress and Disease
- Advanced Algebra and Geometry
- RNA regulation and disease
- Retinal Development and Disorders
- Migraine and Headache Studies
- Cerebrovascular and genetic disorders
- Occupational and environmental lung diseases
- Algebraic Geometry and Number Theory
- Amino Acid Enzymes and Metabolism
- DNA Repair Mechanisms
- Neurological disorders and treatments
- Photosynthetic Processes and Mechanisms
- RNA modifications and cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Research and Splicing
- Genomics and Rare Diseases
- Metabolomics and Mass Spectrometry Studies
- Erythrocyte Function and Pathophysiology
Istituto delle Scienze Neurologiche di Bologna
2012-2025
University of Bologna
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2024
Institute of Neurological Sciences
2012-2024
University of Rochester Medical Center
2024
Ospedale San Pietro Fatebenefratelli
2023-2024
University of Verona
2024
University of Milan
2020
Ospedale Maggiore
2020
University of Pisa
2020
Mutations in OPA1, a dynamin-related GTPase involved 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 the OPA1 gene can also be responsible for syndromic form DOA associated with sensorineural deafness, ataxia, axonal sensory-motor polyneuropathy, chronic progressive external...
Additional neurological features have recently been described in seven families transmitting pathogenic mutations OPA1, the most common cause of autosomal dominant optic atrophy. However, frequency these syndromal 'dominant atrophy plus' variants and extent involvement not established. In this large multi-centre study 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular complications are OPA1 disease, affect up to 20% all mutational carriers. Bilateral...
Dominant optic atrophy (DOA) is characterized by retinal ganglion cell degeneration leading to neuropathy. A subset of DOA caused mutations in the OPA1 gene, encoding for a dynamin-related GTPase required mitochondrial fusion. The functional consequences patients are still poorly understood. This study investigated effect five different pathogenic on energetic efficiency and network dynamics skin fibroblasts from patients. Although maintained their ATP levels grew galactose medium, i.e....
Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as result of homoplasmic point mutations in complex I subunit genes mitochondrial DNA. It characterized by incomplete penetrance, only some mutation carriers become affected. Thus, the DNA necessary but not sufficient to cause neuropathy. Environmental triggers and genetic modifying factors have been considered explain its variable penetrance. We measured copy number mass indicators blood cells from...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multisystemic autosomal recessive disease due to primary thymidine phosphorylase (TP) deficiency. To restore TP activity, we performed reduced intensity allogeneic stem cell transplantations (alloSCTs) in two patients. In the first, alloSCT failed engraft, but second achieved mixed donor chimerism, which partially restored buffy coat activity and lowered plasma nucleosides. Thus, can correct biochemical abnormalities blood of...
Objective Mounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer with mitochondrial dysfunction, recent emphasis has focused on dynamics quality control. Mitochondrial mtDNA maintenance is another link recently emerged, implicating mutations in the fusion genes OPA1 MFN2 pathogenesis of multisystem syndromes characterized by neurodegeneration accumulation multiple deletions postmitotic tissues. Here, we report 2 Italian families affected dominant chronic...
<h3>Objectives:</h3> Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial syndrome, mostly caused by the 8344A>G DNA mutation. Most of previous studies have been based on single case/family reports or series few patients. The primary aim this study was characterization large cohort patients secondary revision previously published data. <h3>Methods:</h3> Retrospective, database-based (Nation-wide Italian Collaborative Network Mitochondrial Diseases) and systematic...
Optic neuropathy is common in mitochondrial disorders, but poorly characterized Friedreich's ataxia (FRDA), a recessive condition caused by lack of the protein frataxin. We investigated 26 molecularly confirmed FRDA patients studying both anterior and posterior sections visual pathway using new, integrated approach. This included field testing optical coherence tomography (OCT), pattern evoked potentials (P-VEPs) diffusion-weighted imaging. The latter was used to study optic radiation...
Abstract Leber’s hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased biogenesis in unaffected mutation carriers a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking...
Hearing impairment is the second most prevalent clinical feature after optic atrophy in dominant associated with mutations OPA1 gene. In this study we characterized hearing dysfunction OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of subjects, one comprising 11 patients (seven males; age range 13–79 years) carrying inducing haploinsufficiency, other, 10 subjects (three 5–58 missense mutations. Both underwent...
Inherited optic neuropathies include complex phenotypes, mostly driven by mitochondrial dysfunction. We report an atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with DNA (mtDNA) depletion without accumulation of multiple deletions. By whole-exome sequencing, we identified mutations affecting the single-strand binding protein (SSBP1) in 4 families dominant 1 recessive inheritance. show that SSBP1 patient-derived...
Abstract Dominant optic atrophy has been associated with mutations in the OPA1 gene, which encodes for a dynamin‐related GTPase, mitochondrial protein implicated formation and maintenance of network morphology. We used phosphorus magnetic resonance spectroscopy to assess calf muscle oxidative metabolism six patients from two unrelated families carrying c.2708‐2711delTTAG deletion exon 27 gene. The rate postexercise phosphocreatine resynthesis, measure adenosine triphosphate production rate,...
purpose. To characterize the clinical features of childhood-onset Leber's hereditary optic neuropathy (LHON) as defined by a pathogenic mtDNA mutation and age at onset equal to or less than 10 years age. methods. Fifty-six LHON Italian pedigrees including 180 affected individuals were reviewed, 14 18 patients with childhood enrolled. was classified acute bilateral, unilateral, slowly progressive, subclinical, according disease features. All underwent complete ophthalmic examination optical...
Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited blinding disease caused by missense mutations in the mitochondrial DNA (mtDNA). However, incomplete penetrance and predominance of male patients presenting with vision loss suggest that modifying factors play an important role development disease. Evidence from several studies suggests both nuclear modifier genes environmental may be necessary to trigger optic neuropathy individuals harboring LHON-causing mtDNA mutation....
Mutations in the ATP6 gene of mtDNA (mitochondrial DNA) have been shown to cause several different neurological disorders. The product this is ATPase 6, an essential component F1F0-ATPase. In present study we show that function F1F0-ATPase impaired lymphocytes from ten individuals harbouring T8993G point mutation associated with NARP (neuropathy, ataxia and retinitis pigmentosa) Leigh syndrome. We both ATP synthase proton transport activity enzyme correlates amount mutated, ranging 13–94%....