10 results on '"Moroni, Isabella"'
Search Results
2. Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes
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Torraco, Alessandra, Ardissone, Anna, Invernizzi, Federica, Rizza, Teresa, Fiermonte, Giuseppe, Niceta, Marcello, Zanetti, Nadia, Martinelli, Diego, Vozza, Angelo, Verrigni, Daniela, Di Nottia, Michela, Lamantea, Eleonora, Diodato, Daria, Tartaglia, Marco, Dionisi-Vici, Carlo, Moroni, Isabella, Farina, Laura, Bertini, Enrico, Ghezzi, Daniele, and Carrozzo, Rosalba
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- 2017
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3. Encephalopathies with intracranial calcification in children: clinical and genetic characterization
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Tonduti, Davide, Panteghini, Celeste, Pichiecchio, Anna, Decio, Alice, Carecchio, Miryam, Reale, Chiara, Moroni, Isabella, Nardocci, Nardo, Campistol, Jaume, Garcia-Cazorla, Angela, Perez Duenas, Belen, Cerebral Calcification International Study Group, Chiapparini, Luisa, Garavaglia, Barbara, and Orcesi, Simona
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- 2018
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4. Unusual presentations and intrafamilial phenotypic variability in infantile onset Alexander disease
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Tonduti, Davide, Ardissone, Anna, Ceccherini, Isabella, Giaccone, Giorgio, Farina, Laura, and Moroni, Isabella
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- 2016
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5. Biallelic mutations in RNF220 cause laminopathies featuring leukodystrophy, ataxia and deafness.
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Sferra, Antonella, Fortugno, Paola, Motta, Marialetizia, Aiello, Chiara, Petrini, Stefania, Ciolfi, Andrea, Cipressa, Francesca, Moroni, Isabella, Leuzzi, Vincenzo, Pieroni, Luisa, Marini, Federica, Tanguy, Odile Boespflug, Eymard-Pierre, Eleonore, Danti, Federica Rachele, Compagnucci, Claudia, Zambruno, Giovanna, Brusco, Alfredo, Santorelli, Filippo M, Chiapparini, Luisa, and Francalanci, Paola
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UBIQUITIN ligases ,LEUKODYSTROPHY ,MISSENSE mutation ,ATAXIA ,SENSORINEURAL hearing loss ,CARDIOMYOPATHIES - Abstract
Leukodystrophies are a heterogeneous group of rare inherited disorders that mostly involve the white matter of the CNS. These conditions are characterized by primary glial cell and myelin sheath pathology of variable aetiology, which causes secondary axonal degeneration, generally emerging with disease progression. Whole exome sequencing performed in five large consanguineous nuclear families allowed us to identify homozygosity for two recurrent missense variants affecting highly conserved residues of RNF220 as the causative event underlying a novel form of leukodystrophy with ataxia and sensorineural deafness. We report these two homozygous missense variants (p.R363Q and p.R365Q) in the ubiquitin E3 ligase RNF220 as the underlying cause of this novel form of leukodystrophy with ataxia and sensorineural deafness that includes fibrotic cardiomyopathy and hepatopathy as associated features in seven consanguineous families. Mass spectrometry analysis identified lamin B1 as the RNF220 binding protein and co-immunoprecipitation experiments demonstrated reduced binding of both RNF220 mutants to lamin B1. We demonstrate that RNF220 silencing in Drosophila melanogaster specifically affects proper localization of lamin Dm0, the fly lamin B1 orthologue, promotes its aggregation and causes a neurodegenerative phenotype, strongly supporting the functional link between RNF220 and lamin B1. Finally, we demonstrate that RNF220 plays a crucial role in the maintenance of nuclear morphology; mutations in primary skin fibroblasts determine nuclear abnormalities such as blebs, herniations and invaginations, which are typically observed in cells of patients affected by laminopathies. Overall, our data identify RNF220 as a gene implicated in leukodystrophy with ataxia and sensorineural deafness and document a critical role of RNF220 in the regulation of nuclear lamina. Our findings provide further evidence on the direct link between nuclear lamina dysfunction and neurodegeneration. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.
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Pipis, Menelaos, Feely, Shawna M E, Polke, James M, Skorupinska, Mariola, Perez, Laura, Shy, Rosemary R, Laura, Matilde, Morrow, Jasper M, Moroni, Isabella, Pisciotta, Chiara, Taroni, Franco, Vujovic, Dragan, Lloyd, Thomas E, Acsadi, Gyula, Yum, Sabrina W, Lewis, Richard A, Finkel, Richard S, Herrmann, David N, Day, John W, and Li, Jun
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CHARCOT-Marie-Tooth disease ,NATURAL history ,EXPERIMENTAL design ,TEST scoring ,DISEASE duration ,LEUKODYSTROPHY ,ANKLE injuries ,PROTEINS ,DISEASE progression ,WHEELCHAIRS ,RESEARCH ,RESEARCH methodology ,PROGNOSIS ,MEDICAL cooperation ,EVALUATION research ,HYDROLASES ,COMPARATIVE studies ,GENES ,AGE factors in disease ,GENETIC markers ,GENETIC techniques ,LONGITUDINAL method ,ORTHOPEDIC apparatus ,NEUROLOGIC examination - Abstract
Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A, we present an in-depth genotype-phenotype study of the baseline characteristics of patients with CMT2A and longitudinal data (1-2 years) to describe the natural history. A childhood onset of autosomal dominant CMT2A is the most predictive marker of significant disease severity and is independent of the disease duration. When compared to adult onset autosomal dominant CMT2A, it is associated with significantly higher rates of use of ankle-foot orthoses, full-time use of wheelchair, dexterity difficulties and also has significantly higher CMT Examination Score (CMTESv2) and CMT Neuropathy Score (CMTNSv2) at initial assessment. Analysis of longitudinal data using the CMTESv2 and its Rasch-weighted counterpart, CMTESv2-R, show that over 1 year, the CMTESv2 increases significantly in autosomal dominant CMT2A (mean change 0.84 ± 2.42; two-tailed paired t-test P = 0.039). Furthermore, over 2 years both the CMTESv2 (mean change 0.97 ± 1.77; two-tailed paired t-test P = 0.003) and the CMTESv2-R (mean change 1.21 ± 2.52; two-tailed paired t-test P = 0.009) increase significantly with respective standardized response means of 0.55 and 0.48. In the paediatric CMT2A population (autosomal dominant and autosomal recessive CMT2A grouped together), the CMT Pediatric Scale increases significantly both over 1 year (mean change 2.24 ± 3.09; two-tailed paired t-test P = 0.009) and over 2 years (mean change 4.00 ± 3.79; two-tailed paired t-test P = 0.031) with respective standardized response means of 0.72 and 1.06. This cross-sectional and longitudinal study of the largest CMT2A cohort reported to date provides guidance for variant interpretation, informs prognosis and also provides natural history data that will guide clinical trial design. [ABSTRACT FROM AUTHOR]
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- 2020
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7. RARS1‐related hypomyelinating leukodystrophy: Expanding the spectrum.
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Mendes, Marisa I., Green, Lydia M. C., Bertini, Enrico, Tonduti, Davide, Aiello, Chiara, Smith, Desiree, Salsano, Ettore, Beerepoot, Shanice, Hertecant, Jozef, Spiczak, Sarah, Livingston, John H., Emrick, Lisa, Fraser, Jamie, Russell, Laura, Bernard, Genevieve, Magri, Stefania, Di Bella, Daniela, Taroni, Franco, Koenig, Mary K., and Moroni, Isabella
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LEUKODYSTROPHY ,CEREBRAL atrophy ,COGNITION disorders ,NUCLEOTIDE sequencing ,AMINO acids ,WESTERN immunoblotting - Abstract
Objective: Biallelic variants in RARS1, encoding the cytoplasmic tRNA synthetase for arginine (ArgRS), cause a hypomyelinating leukodystrophy. This study aimed to investigate clinical, neuroradiological and genetic features of patients with RARS1‐related disease, and to identify possible genotype‐phenotype relationships. Methods: We performed a multinational cross‐sectional survey among 20 patients with biallelic RARS1 variants identified by next‐generation sequencing techniques. Clinical data, brain MRI findings and genetic results were analyzed. Additionally, ArgRS activity was measured in fibroblasts of four patients, and translation of long and short ArgRS isoforms was quantified by western blot. Results: Clinical presentation ranged from severe (onset in the first 3 months, usually with refractory epilepsy and early brain atrophy), to intermediate (onset in the first year with nystagmus and spasticity), and mild (onset around or after 12 months with minimal cognitive impairment and preserved independent walking). The most frequent RARS1 variant, c.5A>G, led to mild or intermediate phenotypes, whereas truncating variants and variants affecting amino acids close to the ArgRS active centre led to severe phenotypes. ArgRS activity was significantly reduced in three patients with intermediate and severe phenotypes; in a fourth patient with intermediate to severe presentation, we measured normal ArgRS activity, but found translation mainly of the short instead of the long ArgRS isoform. Interpretation: Variants in RARS1 impair ArgRS activity and do not only lead to a classic hypomyelination presentation with nystagmus and spasticity, but to a wide spectrum, ranging from severe, early‐onset epileptic encephalopathy with brain atrophy to mild disease with relatively preserved myelination. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutières syndrome.
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Tonduti, Davide, Orcesi, Simona, Jenkinson, Emma M., Dorboz, Imen, Renaldo, Florence, Panteghini, Celeste, Rice, Gillian I., Henneke, Marco, Livingston, John H., Elmaleh, Monique, Burglen, Lydie, Willemsen, Michèl A.A.P., Chiapparini, Luisa, Garavaglia, Barbara, Rodriguez, Diana, Boespflug-Tanguy, Odile, Moroni, Isabella, and Crow, Yanick J.
- Abstract
Background Cystic leukoencephalopathy without megalencephaly is a disorder related in some cases to RNASET2 mutations and characterized by bilateral anterior temporal subcortical cysts and multifocal lobar white matter lesions with sparing of central white matter structures. This phenotype significantly overlaps with the sequelae of in utero cytomegalovirus (CMV) infection, including the presence of intracranial calcification in some cases. Aicardi-Goutières syndrome (AGS) is another inherited leukodystrophy with cerebral calcification mimicking congenital infection. Clinical, radiological and biochemical criteria for the diagnosis of AGS have been established, although the breadth of phenotype associated with mutations in the AGS-related genes is much greater than previously envisaged. Patients and Methods We describe the clinical, biochemical and radiological findings of five patients demonstrating a phenotype reminiscent of AGS. Results All patients were found to carry biallelic mutations of RNASET2 . Conclusions Our patients illustrate the clinical and radiological overlap that can be seen between RNASET2 -related leukodystrophy and AGS in some cases. Our data highlight the need to include both disorders in the same differential diagnosis, and hint at possible shared pathomechanisms related to auto-inflammation which are worthy of further investigation. [ABSTRACT FROM AUTHOR]
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- 2016
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9. Alexander disease evolution over time: data from an Italian cohort of pediatric-onset patients.
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Mura, Eleonora, Nicita, Francesco, Masnada, Silvia, Battini, Roberta, Ticci, Chiara, Montomoli, Martino, Berardinelli, Angela, Pantaleoni, Chiara, Ardissone, Anna, Foiadelli, Thomas, Tartara, Elena, Salsano, Ettore, Veggiotti, Pierangelo, Ceccherini, Isabella, Moroni, Isabella, Bertini, Enrico, and Tonduti, Davide
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GLIAL fibrillary acidic protein , *CHILD patients , *ADOLESCENCE , *MILD cognitive impairment , *PROGNOSIS - Abstract
Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by dominant variants in the Glial Fibrillary Acidic Protein gene. Three main classifications are currently used, the traditional one defined by the age of onset, and two more recent ones based on both clinical features at onset and brain MRI findings. In this study, we retrospectively included patients with genetically confirmed pediatric-onset AxD. Twenty-one Italian patients were enrolled, and we revised all their clinical and radiological data. Participants were divided according to the current classification systems. We qualitatively analyzed data on neurodevelopment and neurologic decline in order to identify the possible trajectories of the evolution of the disease over time. One patient suffered from a Neonatal presentation and showed a rapidly evolving course which led to death within the second year of life (Type Ia). 16 patients suffered from the Infantile presentation: 5 of them (here defined Type Ib) presented developmental delay and began to deteriorate by the age of 5. A second group (Type Ic) included patients who presented a delay in neuromotor development and started deteriorating after 6 years of age. A third group (Type Id) included patients who presented developmental delay and remained clinically stable beyond adolescence. In 4 patients, the age at last evaluation made it not possible to ascertain whether they belonged to Type Ic or Id, as they were too young to evaluate their neurologic decline. 4 patients suffered from the Juvenile presentation: they had normal neuromotor development with no or only mild cognitive impairment; the subsequent clinical evolution was similar to Type Ic AxD in 2 patients, to Id group in the other 2. In conclusion, our results confirm previously described findings about clinical features at onset; based on follow-up data we might classify patients with Type I AxD into four subgroups (Ia, Ib, Ic, Id). Further studies will be needed to confirm our results and to better highlight the existence of clinical and neuroradiological prognostic factors able to predict disease progression. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Spontaneous MRI improvement and absence of cerebral calcification in Aicardi-Goutières syndrome: Diagnostic and disease-monitoring implications.
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Tonduti, Davide, Izzo, Giana, D'Arrigo, Stefano, Riva, Daria, Moroni, Isabella, Zorzi, Giovanna, Cavallera, Vanessa, Pichiecchio, Anna, Uggetti, Carla, Veggiotti, Pierangelo, Orcesi, Simona, Chiapparini, Luisa, and Parazzini, Cecilia
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CEREBRAL circulation , *TYPE I interferons , *CALCIFICATION , *CEREBRAL atrophy , *THERAPEUTICS , *SYNDROMES - Abstract
Aicardi-Goutières syndrome (AGS) is a rare genetic leukoencephalopathy related to inappropriate activation of type I interferon. Neuroradiological findings are typically characterized by white matter abnormalities, cerebral atrophy and cerebral calcification. The disease usually manifests itself during the first year of life in the form of an initial "encephalitic-like" phase followed by a chronic phase of stabilization of the neurological signs. Recently new therapeutic strategies have been proposed aimed at blocking the abnormal activation of the interferon cascade. We reviewed clinical and MRI findings in three young RNASEH2B -mutated patients studied with serial CT and MRI studies. All three patients presented clinical and MRI features consistent with AGS but, very unexpectedly, an improving neuroradiological course. In patient 1, the MRI improvement was noted some months after treatment with high-dose steroid and IVIg treatment; in patients 2 and 3 it occurred spontaneously. Patient 2 did not show cerebral calcification on CT images. Our series highlights the possibility of spontaneous neuroradiological improvement in AGS2 patients, as well as the possibility of absence of cerebral calcification in AGS. The study underlines the need for extreme caution when using MRI as an outcome measure in therapeutic trials specific for this disease. MRI follow-up studies in larger series are necessary to describe the natural course of AGS. [ABSTRACT FROM AUTHOR]
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- 2019
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