A5002783856- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Aquaculture Nutrition and Growth
- Physiological and biochemical adaptations
- Neurogenetic and Muscular Disorders Research
- Renin-Angiotensin System Studies
- Ubiquitin and proteasome pathways
- Liver Disease Diagnosis and Treatment
- Hereditary Neurological Disorders
- Nuclear Structure and Function
- Inflammatory Myopathies and Dermatomyositis
- Cytomegalovirus and herpesvirus research
- Lysosomal Storage Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Glycogen Storage Diseases and Myoclonus
- Amyotrophic Lateral Sclerosis Research
- Genetic Syndromes and Imprinting
- Diabetes and associated disorders
- Autoimmune Neurological Disorders and Treatments
- RNA modifications and cancer
- Peripheral Neuropathies and Disorders
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2011-2025
Ospedale Amedeo di Savoia
2022-2023
Ospedale Maggiore
1998-2023
Azienda di Rilievo Nazionale ed Alta Specializzazione
2022
University of Ferrara
2021
University of Milan
1998-2015
Urology Foundation
2014
University College London
2014
MRC Laboratory for Molecular Cell Biology
2014
University of Pavia
2014
Abstract An out‐of‐frame mutation of the mitochondrial DNA‐encoded subunit I cytochrome c oxidase (COX) was discovered during investigation a severe isolated muscle COX deficiency in patient with motor neuron‐like degeneration. The is heteroplasmic 5‐bp microdeletion located 5′ end COI gene, leading to premature termination corresponding translation product. Western blot analysis, immunohistochemistry, and single‐fiber polymerase chain reaction demonstrated tight correlation between defect,...
<b>Objective: </b> To describe the unique combination of partial depletion and multiple deletions mitochondrial DNA (mtDNA) on muscle analysis three siblings with neurogastrointestinal encephalomyopathy (MNGIE). <b>Background: MNGIE is a relatively homogeneous autosomal recessive disorder characterized by gastrointestinal dysmobility, ophthalmoparesis, peripheral neuropathy, myopathy, altered white matter signal at brain imaging. Muscle mtDNA have been found in about half described cases....
<b>Background:</b> The axonal forms of Charcot-Marie-Tooth (CMT2) disease are a clinically and genetically heterogeneous group disorders. Mitofusin 2 gene (<i>MFN2</i>) mutations the most common cause CMT2. Complex phenotypes have been described in association with <i>MFN2</i> mutations, including CMT2 pyramidal features (hereditary motor sensory neuropathy [HSMN V]) optic atrophy (HMSN VI). <b>Objective:</b> To report on clinical, neurophysiologic, neuropathologic an Italian family novel...
Autosomal dominant progressive external ophthalmoplegia (adPEO) is caused by mutations in at least three different genes: <i>ANT1</i> (chromosome 4q34–35), <i>TWINKLE</i>, and <i>POLG</i>. The gene encodes the adenine nucleotide translocator-1 (ANT1). We identified a heterozygous T293C mutation of Greek family with adPEO. resulting leucine to proline substitution likely modifies secondary structure ANT1 protein. may account for adPEO families ethnic backgrounds.
Limb-girdle muscular dystrophy (LGMD) 2L, caused by mutations in the anoctamin 5 (ANO5) gene, is third most common LGMD Northern and Central Europe, where c.191dupA mutation causes majority of cases. We evaluated data from 228 Italian patients to determine prevalence LGMD2L mutation, describe clinical, muscle biopsy, magnetic resonance imaging findings these patients. Forty-three who lacked molecular diagnosis were studied for ANO5 mutations, four novel found three probands. Only one proband...
Abstract Mitochondria change distribution across cells following a variety of pathophysiological stimuli. The mechanisms presiding over this redistribution are yet undefined. In murine model overexpressing Drp1 specifically in skeletal muscle, we find marked mitochondria repositioning muscle fibres and demonstrate that is involved process. binds KLC1 enhances microtubule-dependent transport mitochondria. Drp1-KLC1 coupling triggers the displacement KIF5B from kinesin-1 complex increasing its...
Charcot-Marie-Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, transmembrane protein of the outer mitochondrial membrane. We performed cross-sectional analysis on thirteen patients carrying MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated presented variable age onset wide phenotypic spectrum, with most presenting severe phenotype. A novel heterozygous missense variant was...
DNM2 encodes the dynamin-2 protein, a GTPase involved in clathrin-mediated endocytosis and other membrane trafficking pathways. The protein is composed of several functional domains, including domain, middle pleckstrin homology (PH) effector domain (GED), proline-rich domain. Monoallelic variants are associated with Charcot-Marie-Tooth disease rare form congenital centronuclear myopathy (CNM). Several have been reported patients CNM, typically presenting mild slowly progressive symptoms. We...
To identify the genetic cause of a complex syndrome characterized by autophagic vacuolar myopathy (AVM), hypertrophic cardiomyopathy, pigmentary retinal degeneration, and epilepsy.Clinical, pathologic, study.Two brothers presented with visual failure, seizures, prominent cardiac involvement, but only mild cognitive impairment no motor deterioration after 40 years disease duration. Muscle biopsy revealed presence widespread alterations suggestive AVM vacuoles sarcolemmal features. Through...
The definition of cell metabolic profile is essential to ensure skeletal muscle fiber heterogeneity and achieve a proper equilibrium between the self-renewal commitment satellite stem cells. Heme sustains several biological functions, including processes profoundly implicated with metabolism. significant heme-producing body compartment, but consequences impaired heme homeostasis on this tissue have been poorly investigated. Here, we generate skeletal-muscle-specific feline leukemia virus...
Collagen VI is a heterotrimeric protein expressed in several tissues and involved the maintenance of cell integrity. It localizes at surface, creating microfilamentous network that links cytoskeleton to extracellular matrix. The heterotrimer consists three chains encoded by COL6A1, COL6A2 COL6A3 genes. Recessive dominant molecular defects cause two main disorders, severe Ullrich congenital muscular dystrophy relatively mild slowly progressive Bethlem myopathy. We analyzed clinical aspects,...
<b><i>Background/Objective:</i></b> Apoptosis, or programmed cell death, is an evolutionary conserved mechanism essential for morphogenesis and tissue homeostasis, but it plays important role also in pathologic conditions, including neurologic disorders. Its execution pathway critically regulated at the mitochondrial level. Evidence of apoptosis muscle specimens was investigated patients with genetically defined encephalomyopathies. <b><i>Methods:</i></b> Thirty-three biopsies from...
Hypertriglyceridemia is a common feature of metabolic syndrome (MetS), as well non-alcoholic fatty liver disease (NAFLD), which considered the hepatic manifestation MetS. Fat accumulation in hepatocytes may alter mitochondrial homeostasis predisposing to advanced disease. Here, we report case 40-year-old woman with early aggressive NAFLD due severe hypertriglyceridemia that ensued from combination genetic variants and additional risk factors. Genetic screening was performed by using...
Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast ( TNNI2 ) TnI-slow TNNI1 ), are predominantly expressed in fast- slow-twitch myofibers, respectively. variants a rare cause of arthrogryposis, whereas have not been conclusively established to skeletal myopathy. We identified recessive loss-of-function as well dominant gain-of-function disease, each with distinct physiological consequences disease mechanisms. three families biallelic (F1:...