15 results on '"Chiara Panicucci"'
Search Results
2. Early Muscle MRI Findings in a Pediatric Case of Emery-Dreifuss Muscular Dystrophy Type 1
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Chiara Panicucci, Sara Casalini, Monica Traverso, Noemi Brolatti, Serena Baratto, Lizzia Raffaghello, Marina Pedemonte, Luca Doglio, Maria Derchi, Giorgio Tasca, Beatrice M. Damasio, Chiara Fiorillo, and Claudio Bruno
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Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,General Medicine - Abstract
Emery-Dreifuss muscular dystrophy (EDMD) is a rare disease characterized by early contractures, progressive muscle weakness, and cardiac abnormalities. Different subtypes of EDMD have been described, with the two most common forms represented by the X-linked EDMD1, caused by mutations in the EMD gene encoding emerin, and the autosomal EDMD2, due to mutations in the LMNA gene encoding lamin A/C. A clear definition of the magnetic resonance imaging (MRI) pattern in the two forms, and especially in the rarer EDMD1, is still lacking, although a preferential involvement of the medial head of the gastrocnemius has been suggested in EDMD2. We report a 13-year-old boy with mild limb girdle muscle weakness, elbow and ankle contractures, with absence of emerin at muscle biopsy, carrying a hemizygous frameshift mutation on the EMD gene (c.153dupC/p.Ser52Glufs*9) of maternal inheritance. Minor cardiac rhythm abnormalities were detected at 24-hour Holter electrocardiogram and required β-blocker therapy. MRI scan of the thighs showed a mild diffuse involvement, while tibialis anterior, extensor digitorum longus, peroneus longus, and medial gastrocnemius were the most affected muscles in the leg. We also provide a review of the muscular MRI data in EDMD patients and highlight the relative heterogeneity of the MRI patterns found in EDMDs, suggesting that muscle MRI should be studied in larger EDMD cohorts to better define disease patterns and to cover the wide disease spectrum.
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- 2023
3. The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment
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Chiara Fiorillo, Giovanna Capodivento, Alessandro Geroldi, Stefano Tozza, Isabella Moroni, Payam Mohassel, Matteo Cataldi, Chiara Campana, Simone Morando, Chiara Panicucci, Marina Pedemonte, Noemi Brolatti, Sabrina Siliquini, Monica Traverso, Serena Baratto, Doriana Debellis, Stefania Magri, Valeria Prada, Emilia Bellone, Vincenzo Salpietro, Sandra Donkervoort, Kenneth Gable, Sita D. Gupta, Teresa M. Dunn, Carsten G. Bönnemann, Franco Taroni, Claudio Bruno, Angelo Schenone, Paola Mandich, Lucilla Nobbio, and Maria Nolano
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l-serine ,Sphingolipids ,Histology ,SPTLC1 ,Serine C-Palmitoyltransferase ,Peripheral Nervous System Diseases ,Pathology and Forensic Medicine ,HSAN ,Neurology ,Physiology (medical) ,Mutation ,Serine ,Humans ,S331 ,motor neuron ,sphingolipids ,Neurology (clinical) ,Hereditary Sensory and Autonomic Neuropathies ,Motor Neuron Disease - Abstract
SPTLC1-related disorder is a late onset sensory-autonomic neuropathy associated with perturbed sphingolipid homeostasis which can be improved by supplementation with the serine palmitoyl-CoA transferase (SPT) substrate, l-serine. Recently, a juvenile form of motor neuron disease has been linked to SPTLC1 variants. Variants affecting the p.S331 residue of SPTLC1 cause a distinct phenotype, whose pathogenic basis has not been established. This study aims to define the neuropathological and biochemical consequences of the SPTLC1 p.S331 variant, and test response to l-serine in this specific genotype.We report clinical and neurophysiological characterisation of two unrelated children carrying distinct p.S331 SPTLC1 variants. The neuropathology was investigated by analysis of sural nerve and skin innervation. To clarify the biochemical consequences of the p.S331 variant, we performed sphingolipidomic profiling of serum and skin fibroblasts. We also tested the effect of l-serine supplementation in skin fibroblasts of patients with p.S331 mutations.In both patients, we recognised an early onset phenotype with prevalent progressive motor neuron disease. Neuropathology showed severe damage to the sensory and autonomic systems. Sphingolipidomic analysis showed the coexistence of neurotoxic deoxy-sphingolipids with an excess of canonical products of the SPT enzyme. l-serine supplementation in patient fibroblasts reduced production of toxic 1-deoxysphingolipids but further increased the overproduction of sphingolipids.Our findings suggest that p.S331 SPTLC1 variants lead to an overlap phenotype combining features of sensory and motor neuropathies, thus proposing a continuum in the spectrum of SPTLC1-related disorders. l-serine supplementation in these patients may be detrimental.
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- 2022
4. Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study
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Aurora Fusto, Denise Cassandrini, Chiara Fiorillo, Valentina Codemo, Guja Astrea, Adele D’Amico, Lorenzo Maggi, Francesca Magri, Marika Pane, Giorgio Tasca, Daniele Sabbatini, Luca Bello, Roberta Battini, Pia Bernasconi, Fabiana Fattori, Enrico Silvio Bertini, Giacomo Comi, Sonia Messina, Tiziana Mongini, Isabella Moroni, Chiara Panicucci, Angela Berardinelli, Alice Donati, Vincenzo Nigro, Antonella Pini, Melania Giannotta, Claudia Dosi, Enzo Ricci, Eugenio Mercuri, Giovanni Minervini, Silvio Tosatto, Filippo Santorelli, Claudio Bruno, Elena Pegoraro, Fusto, Aurora, Cassandrini, Denise, Fiorillo, Chiara, Codemo, Valentina, Astrea, Guja, D'Amico, Adele, Maggi, Lorenzo, Magri, Francesca, Pane, Marika, Tasca, Giorgio, Sabbatini, Daniele, Bello, Luca, Battini, Roberta, Bernasconi, Pia, Fattori, Fabiana, Bertini, Enrico Silvio, Comi, Giacomo, Messina, Sonia, Mongini, Tiziana, Moroni, Isabella, Panicucci, Chiara, Berardinelli, Angela, Donati, Alice, Nigro, Vincenzo, Pini, Antonella, Giannotta, Melania, Dosi, Claudia, Ricci, Enzo, Mercuri, Eugenio, Minervini, Giovanni, Tosatto, Silvio, Santorelli, Filippo, Bruno, Claudio, and Pegoraro, Elena
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Myopathy ,Genotype–phenotype correlations ,Neuromuscular disorder ,Central core disease ,Multi-minicore disease ,Protein modelling ,RYR1-related myopathies ,Humans ,Muscle, Skeletal ,Mutation ,Myopathies, Structural, Congenital ,Myopathy, Central Core ,Ryanodine Receptor Calcium Release Channel ,Pathology and Forensic Medicine ,Cellular and Molecular Neuroscience ,Congenital ,Structural ,Genotype–phenotype correlation ,Skeletal ,musculoskeletal system ,Settore MED/26 - NEUROLOGIA ,Muscle ,Myopathies ,Neurology (clinical) ,tissues ,Central Core - Abstract
Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.
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- 2022
5. Genetic modifiers of upper limb function in Duchenne muscular dystrophy
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Daniele Sabbatini, Aurora Fusto, Sara Vianello, Matteo Villa, Joanna Janik, Grazia D’Angelo, Eleonora Diella, Francesca Magri, Giacomo P. Comi, Chiara Panicucci, Claudio Bruno, Adele D’Amico, Enrico Bertini, Guja Astrea, Roberta Battini, Luisa Politano, Riccardo Masson, Giovanni Baranello, Stefano C. Previtali, Sonia Messina, Gianluca Vita, Angela Berardinelli, Tiziana Mongini, Antonella Pini, Marika Pane, Eugenio Mercuri, Eric P. Hoffman, Lauren Morgenroth, Heather Gordish-Dressman, Tina Duong, Craig M. McDonald, Luca Bello, and Elena Pegoraro
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Duchenne muscular dystrophy ,Genetic modifiers ,Genotype ,CD40 ,SPP1–osteopontin ,Upper limb function ,Actinin ,Cohort Studies ,Humans ,Quality of Life ,Upper Extremity ,Muscular Dystrophy, Duchenne ,Duchenne ,Neurology ,Settore MED/26 - Neurologia ,Neurology (clinical) ,Muscular Dystrophy - Abstract
Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations.
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- 2022
6. The Role of Muscle Biopsy in Diagnostic Process of Infant Hypotonia: From Clinical Classification to the Genetic Outcome
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Marina Pedemonte, Claudio Bruno, Raffaele Falsaperla, Chiara Fiorillo, Mattia Pacetti, Andrea Moscatelli, Alice Donati, Marco Veneruso, Paolo Broda, Maria Margherita Mancardi, Luca A. Ramenghi, Carlo Minetti, Chiara Panicucci, Salvatore Savasta, Gianluca Piatelli, Lino Nobili, M. Traverso, and Serena Baratto
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muscular dystrophy ,medicine.medical_specialty ,congenital myopathy ,Biopsy ,medicine ,Sampling (medicine) ,Muscular dystrophy ,RC346-429 ,Floppy Infant ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,genetic outcome ,Brief Research Report ,medicine.disease ,floppy infant ,Congenital myopathy ,Hypotonia ,Neurology ,Histopathology ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,Radiology ,muscle biopsy ,medicine.symptom ,business - Abstract
The role of muscle biopsy in the diagnostic workup of floppy infants is controversial. Muscle sampling is invasive, and often, results are not specific. The rapid expansion of genetic approach has made the muscle histopathology analysis less crucial. This study aims to assess the role and efficacy of muscle histopathology in the diagnostic algorithm of hypotonia in early infancy through a retrospective analysis of 197 infants who underwent muscle biopsy in their first 18 months of life. Data analysis revealed that 92/197 (46.7%) of muscle biopsies were non-specific (80) or normal (12), not allowing a specific diagnosis. In 41/197 (20.8%) cases, biopsy suggested a metabolic or mitochondrial myopathy, while in 23/197 cases (11.7%), we found evidence of muscular dystrophy. In 19/197 cases (9.7%), histopathology characteristics of a congenital myopathy were reported. In 22/197 cases (11.7%), the histopathological study indicated presence of a neurogenic damage. Overall, 46 diagnoses were then achieved by oriented genetic tests. Muscle biopsy results were consistent with genetic results in 90% of cases. Diagnostic algorithms for the diagnosis of a floppy infant are largely missing. Muscle biopsy alone can lead to a diagnosis, help the clinician in the choice of a genetic test, or even modify a diagnosis made previously.
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- 2021
7. LGMD
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Lidia Gonzalez-Quereda, Claudio Bruno, E. Dourado, Juan J. Vílchez, Chiara Panicucci, M. Guglierir, N. Kadem, Jorge Alonso-Pérez, Nuria Muelas, Afagh Alavi, M. Umair, Chiara Marini-Bettolo, Edmar Zanoteli, V. Straub, and J. Diaz-Manera
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Pathology ,medicine.medical_specialty ,Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,Neurology (clinical) ,Muscular dystrophy ,medicine.disease ,business ,Genetics (clinical) ,Delta-Sarcoglycan ,Large cohort - Published
- 2021
8. Muscle inflammatory pattern in alpha- and gamma-sarcoglycanopathies
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Carlo Minetti, Lizzia Raffaghello, Chiara Panicucci, Chiara Fiorillo, Stefano C. Previtali, Serena Baratto, Claudio Bruno, Monica Traverso, Elena Pegoraro, Adele D'Amico, Paola Tonin, and Giorgio Tasca
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musculoskeletal diseases ,Duchenne muscular dystrophy ,Genetic enhancement ,Biopsy ,Cell ,Alpha (ethology) ,Major histocompatibility complex ,Muscular Dystrophies ,Pathology and Forensic Medicine ,Pathogenesis ,Immune system ,medicine ,Sarcoglycanopathies ,Humans ,Muscle, Skeletal ,biology ,Myositis ,business.industry ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Neurology ,Immunology ,biology.protein ,Neurology (clinical) ,business - Abstract
Aim Since the immune system plays a role in the pathogenesis of several muscular dystrophies, we aim to characterize several muscular inflammatory features in α- (LGMD R3) and γ-sarcoglycanopathies (LGMD R5). Materials and methods We explored the expression of major histocompatibility complex class I molecules (MHCI), and we analyzed the composition of the immune infiltrates in muscle biopsies from 10 patients with LGMD R3 and 8 patients with LGMD R5, comparing the results to Duchenne muscular dystrophy patients (DMD). Results A consistent involvement of the immune response was observed in sarcoglycanopathies, although it was less evident than in DMD. LGMD R3-R5 and DMD shared an abnormal expression of MHCI, and the composition of the muscular immune cell infiltrate was comparable. Conclusion These findings might serve as a rationale to fine-tune a disease-specific immunomodulatory regimen, particularly relevant in view of the rapid development of gene therapy for sarcoglycanopathies.
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- 2021
9. Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
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Afagh Alavi, Yalda Nilipour, Luca Bello, Jorge Alonso-Pérez, Shahriar Nafissi, Muhammad Umair, Lidia Gonzalez-Quereda, Mario Emilio Dourado, Chiara Marini-Bettolo, Chiara Panicucci, Xavier Suárez-Calvet, Gultekin Kutluk, Kinga Hadzsiev, Lucas Michielon de Augusto Isihi, Edmar Zanoteli, Jordi Díaz-Manera, Thomas O. Crawford, Muhammad Younus, Ana Töpf, Naz Kadem, Elena Pegorano, Juan José Vilchez, Claudio Bruno, Pia Gallano, Béla Melegh, Michela Guglieri, Nuria Muelas, and Volker Straub
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Adult ,medicine.medical_specialty ,Weakness ,Proximal muscle weakness ,Muscular dystrophies ,Generalized muscle weakness ,SGCD ,Muscular Dystrophies ,SGCG ,Sarcoglycans ,Internal medicine ,Sarcoglycanopathies ,medicine ,Humans ,Registries ,Muscular dystrophy ,Child ,Retrospective Studies ,LGMD-R6/2F ,Muscle Weakness ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,Delta-sarcoglycan ,Retrospective cohort study ,medicine.disease ,Muscular Dystrophies, Limb-Girdle ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy. Alonso-Pérez et al. describe the largest cohort to date of patients with the ultra-rare neuromuscular disorder delta-sarcoglycanopathy, and show that the severity and rate of progressive weakness correlates inversely with the abundance of protein expression on muscle biopsy.
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- 2021
10. New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy patients
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Laura Costa-Comellas, Chiara Panicucci, Ana Camacho-Salas, Ulrike Schara, Claudio Semplicini, Isabel Illa, Arturo Fraga-Bau, Leroy ten Dam, Jan De Bleecker, Lea Leonardis, Jesper Helbo Storgaard, Juan Carlos de Leon-Hernández, Vittoria Zangaro, Giacomo P. Comi, Vincenzo Nigro, Adele D'Amico, Benedikt Schoser, Pia Gallano, Manuela Santos, Edoardo Malfatti, Cristina Domínguez-González, F. Munell, De Vos Elke, Alicia Alonso-Jimenez, Matteo Garibaldi, Bjarne Udd, Nicoline Løkken, A. J. van der Kooi, Giorgio Tasca, John Vissing, Jordi Díaz-Manera, Elena Pegoraro, Andrea Gangfuß, Jorge Alonso-Pérez, Claudia Weiss, Luisa Politano, Marie Rohlenová, Cristina Garrido, David Gómez-Andrés, Jana Haberlová, Roberto Fernández-Torrón, Gabriele Dekomien, Kristl G. Claeys, Marianne de Visser, Andrés Nascimento, Michela Guglieri, Carlos Ortez, Isabelle Richard, Lidia Gonzalez-Quereda, Béla Melegh, Claudio Bruno, Omar Abdel-Mannan, Anna Sarkozy, Adolfo López de Munain, Blaz Koritnik, Nicolas Deconinck, Kinga Hadzsiev, Luca Bello, Johanna Palmio, Volker Straub, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Neurology, ANS - Neuroinfection & -inflammation, Graduate School, Alonso-Pérez, Jorge, González-Quereda, Lidia, Bello, Luca, Guglieri, Michela, Straub, Volker, Gallano, Pia, Semplicini, Claudio, Pegoraro, Elena, Zangaro, Vittoria, Nascimento, André, Ortez, Carlo, Comi, Giacomo Pietro, ten Dam, Leroy, De Visser, Marianne, van der Kooi, A J, Garrido, Cristina, Santos, Manuela, Schara, Ulrike, Gangfuß, Andrea, Løkken, Nicoline, Storgaard, Jesper Helbo, Vissing, John, Schoser, Benedikt, Dekomien, Gabriele, Udd, Bjarne, Palmio, Johanna, D'Amico, Adele, Politano, Luisa, Nigro, Vincenzo, Bruno, Claudio, Panicucci, Chiara, Sarkozy, Anna, Abdel-Mannan, Omar, Alonso-Jimenez, Alicia, Claeys, Kristl G, Gomez-Andrés, David, Munell, Francina, Costa-Comellas, Laura, Haberlová, Jana, Rohlenová, Marie, Elke, De Vo, De Bleecker, Jan L, Dominguez-González, Cristina, Tasca, Giorgio, Weiss, Claudia, Deconinck, Nicola, Fernández-Torrón, Roberto, López de Munain, Adolfo, Camacho-Salas, Ana, Melegh, Béla, Hadzsiev, Kinga, Leonardis, Lea, Koritnik, Blaz, Garibaldi, Matteo, de Leon-Hernández, Juan Carlo, Malfatti, Edoardo, Fraga-Bau, Arturo, Richard, Isabelle, Illa, Isabel, and Díaz-Manera, Jordi
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0301 basic medicine ,Registrie ,Male ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,Medizin ,Limb girdle muscular dystrophie ,Cohort Studies ,0302 clinical medicine ,Registries ,Child ,sarcoglycan ,ComputingMilieux_MISCELLANEOUS ,treatment ,Cohort ,cohort ,Middle Aged ,limb girdle muscular dystrophies ,3. Good health ,Europe ,Child, Preschool ,registries ,Female ,Cohort study ,Sarcoglycanopathies ,Adult ,medicine.medical_specialty ,Adolescent ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Humans ,Limb girdle muscular dystrophies ,Sarcoglycan ,Genetic Association Studies ,SGCA ,Aged ,Retrospective Studies ,business.industry ,Retrospective cohort study ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,medicine.disease ,Treatment ,030104 developmental biology ,Sarcoglycanopathy ,Muscular Dystrophies, Limb-Girdle ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Neurology (clinical) ,Human medicine ,Age of onset ,business ,030217 neurology & neurosurgery ,Limb-girdle muscular dystrophy - Abstract
Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3–6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.
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- 2020
11. Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism
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Rasha Al-Khalidi, Krzysztof Zabłocki, Stephen Arkle, Kameshwari Ambati, Dariusz C. Górecki, Natalia Chira, Rhiannon E. McGeehan, Claudio Bruno, Paul A. Cox, Justyna Róg, Elisabetta Gazzerro, Christopher N. J. Young, Jayakrishna Ambati, and Chiara Panicucci
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Male ,Models, Molecular ,0301 basic medicine ,Antimetabolites ,Duchenne muscular dystrophy ,Purinergic Receptors ,APC-PAID ,Pharmacology ,P2RX7 ,lcsh:RC346-429 ,Myoblasts ,Mice ,Adenosine Triphosphate ,Myocyte ,Creatine Kinase ,Cells, Cultured ,biology ,Muscles ,3. Good health ,AZT ,medicine.symptom ,Purinergic receptors ,Zidovudine ,mdx ,medicine.drug ,Collagen Type IV ,eATP ,Antigens, Differentiation, Myelomonocytic ,Mice, Transgenic ,Inflammation ,Muscle disorder ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Antigens, CD ,medicine ,Animals ,Muscle Strength ,lcsh:Neurology. Diseases of the nervous system ,Sarcolemma ,business.industry ,Research ,Biomedical Sciences ,medicine.disease ,Muscular Dystrophy, Duchenne ,Disease Models, Animal ,030104 developmental biology ,Mice, Inbred mdx ,biology.protein ,Calcium ,Creatine kinase ,Receptors, Purinergic P2X7 ,Neurology (clinical) ,business - Abstract
Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMDmdx mouse model. As P2RX7 is an attractive target in a range of human diseases, specific antagonists have been developed. Yet, these will require lengthy safety testing in the pediatric population of Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with an established safety record, including in children. We demonstrate here that AZT (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as other antagonists. Moreover, short-term AZT treatment at the peak of disease in DMDmdx mice attenuated the phenotype without any detectable side effects. Recovery was evident in the key parameters such as reduced sarcolemma permeability confirmed by lower serum creatine kinase levels and IgG influx into myofibres, decreased inflammatory cell numbers and inflammation markers in leg and heart muscles of treated mice. Moreover, this short-term therapy had some positive impact on muscle strength in vivo and no detrimental effect on mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly re-purposed for the treatment of this highly debilitating and lethal disease. This approach is not constrained by causative DMD mutations and may be effective in alleviating both muscle and non-muscle abnormalities. Electronic supplementary material The online version of this article (10.1186/s40478-018-0530-4) contains supplementary material, which is available to authorized users.
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- 2018
12. P.266Bone mass acquisition and determinants of bone mineral density and fragility fractures in DMD patients
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Chiara Fiorillo, Giorgia Brigati, Claudio Bruno, Sara Notarnicola, Chiara Panicucci, M. Maghnie, Carlo Minetti, N. Di Iorgi, and Marina Pedemonte
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Bone mineral ,Fragility ,Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,Dentistry ,Medicine ,Neurology (clinical) ,business ,Genetics (clinical) - Published
- 2019
13. SMA CLINICAL DATA, OUTCOME MEASURES AND REGISTRIES
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M. Maghnie, Carlo Minetti, Giorgia Brigati, N. DiIorgi, E. Medone, Chiara Fiorillo, Chiara Panicucci, Claudio Bruno, S. Notarnicola, and Marina Pedemonte
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medicine.medical_specialty ,Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,Outcome measures ,Physical therapy ,Medicine ,Neurology (clinical) ,SMA ,business ,Genetics (clinical) - Published
- 2018
14. EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement
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Carlo Minetti, Francesca Pinto, Denise Cassandrini, Holger Trucks, Marisol Mirabelli-Badenier, Thomas Sander, Filippo M. Santorelli, Rosanna Trovato, Maja Di Rocco, Chiara Panicucci, Roberta Biancheri, Pasquale Striano, Andrea Rossi, Federico Zara, and Marina Pedemonte
- Subjects
Male ,medicine.medical_specialty ,Cerebellum ,Muscle Hypotonia ,Neurology ,Adolescent ,Developmental Disabilities ,DNA Mutational Analysis ,Pontocerebellar hypoplasia ,Nervous System Malformations ,Severity of Illness Index ,medicine ,Humans ,Child ,Exosome Multienzyme Ribonuclease Complex ,business.industry ,RNA-Binding Proteins ,Spinal muscular atrophy ,Anatomy ,medicine.disease ,Magnetic Resonance Imaging ,Pons ,Hypoplasia ,Phenotype ,medicine.anatomical_structure ,Spinal Cord ,nervous system ,Child, Preschool ,Mutation ,Neurology (clinical) ,Cerebellar hypoplasia (non-human) ,business ,Brain Stem - Abstract
Pontocerebellar hypoplasia (PCH) type 1 is characterized by the co-occurrence of spinal anterior horn involvement and hypoplasia of the cerebellum and pons. EXOSC3 has been recently defined as a major cause of PCH type 1. Three different phenotypes showing variable severity have been reported. We identified a homozygous mutation [c.395A > C/p.D132A] in EXOSC3 in four patients with muscle hypotonia, developmental delay, spinal anterior horn involvement, and prolonged survival, consistent with the "mild PCH1 phenotype". Interestingly, isolated cerebellar hypoplasia limited to the hemispheres or involving both hemispheres and vermis was the main neuroradiologic finding, whereas the pontine volume was in the normal range for age. These findings strongly suggest that analysis of the EXOSC3 gene should be recommended also in patients with spinal anterior horn involvement and isolated cerebellar hypoplasia.
- Published
- 2013
15. Surgical correction of scoliosis in patients with congenital myopathies
- Author
-
Marina Pedemonte, Carlo Minetti, A. Andaloro, Federica Trucco, F. Becchetti, Valentina Lanzillotta, Chiara Panicucci, Chiara Fiorillo, and Claudio Bruno
- Subjects
medicine.medical_specialty ,Neurology ,business.industry ,Pediatrics, Perinatology and Child Health ,medicine ,In patient ,Neurology (clinical) ,Scoliosis ,Surgical correction ,medicine.disease ,business ,Genetics (clinical) ,Surgery - Published
- 2015
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