69 results on '"Panteghini C"'
Search Results
2. EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia
- Author
-
Kuipers, D. (Demy), Mandemakers, W.J. (Wim), Lu, C.-S. (Chin-Song), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Fevga, C. (Christina), Tadic, V. (Vera), Carecchio, M. (Miryam), Osterman, B. (Bradley), Sagi-Dain, L. (Lena), Wu-Chou, Y.H. (Yah-Huei), Chen, C.C. (Chiung C.), Chang, H.C. (Hsiu-Chen), Wu, S.-L. (Shey-Lin), Yeh, T.-H. (Tu-Hsueh), Weng, Y.H. (Yi Hsin), Elia, A.E. (Antonio E.), Panteghini, C. (Celeste), Marotta, N. (Nicolas), Pauly, M.G. (Martje G.), Kühn, A.A. (Andrea A.), Volkmann, J. (Jens), Lace, B. (Baiba), Meijer, I.A. (Inge A.), Kandaswamy, K. (Krishna), Quadri, M. (Marialuisa), Garavaglia, B. (Barbara), Lohmann, K. (Katja), Bauer, P. (Peter), Mencacci, N.E. (Niccolo), Lubbe, S.J. (Steven J.), Klein, C. (Christoph), Bertoli Avella, A.M. (Aida), Bonifati, V. (Vincenzo), Kuipers, D. (Demy), Mandemakers, W.J. (Wim), Lu, C.-S. (Chin-Song), Olgiati, S. (Simone), Breedveld, G.J. (Guido), Fevga, C. (Christina), Tadic, V. (Vera), Carecchio, M. (Miryam), Osterman, B. (Bradley), Sagi-Dain, L. (Lena), Wu-Chou, Y.H. (Yah-Huei), Chen, C.C. (Chiung C.), Chang, H.C. (Hsiu-Chen), Wu, S.-L. (Shey-Lin), Yeh, T.-H. (Tu-Hsueh), Weng, Y.H. (Yi Hsin), Elia, A.E. (Antonio E.), Panteghini, C. (Celeste), Marotta, N. (Nicolas), Pauly, M.G. (Martje G.), Kühn, A.A. (Andrea A.), Volkmann, J. (Jens), Lace, B. (Baiba), Meijer, I.A. (Inge A.), Kandaswamy, K. (Krishna), Quadri, M. (Marialuisa), Garavaglia, B. (Barbara), Lohmann, K. (Katja), Bauer, P. (Peter), Mencacci, N.E. (Niccolo), Lubbe, S.J. (Steven J.), Klein, C. (Christoph), Bertoli Avella, A.M. (Aida), and Bonifati, V. (Vincenzo)
- Abstract
Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia. Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients. Results: We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic tra
- Published
- 2020
- Full Text
- View/download PDF
3. Assessment of human enteric viruses in shellfish collected in the Adriatic Sea
- Author
-
Pavoni, E., primary, Losio, M.N., additional, Croci, L., additional, Panteghini, C., additional, Zanardini, N., additional, Maccabiani, G., additional, Tilola, M., additional, D’Abrosca, F., additional, and Boni, P., additional
- Published
- 2006
- Full Text
- View/download PDF
4. Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single‐center cohort study
- Author
-
Carecchio, Miryam, Invernizzi, F., Gonzàlez-Latapi, P., Panteghini, C., Zorzi, G., Romito, L., Leuzzi, V., Galosi, S., Reale, C., Zibordi, F., Joseph, A.P., Topf, Maya, Piano, C., Bentivoglio, A.R., Girotti, F., Morana, P., Morana, B., Kurian, M.A., Garavaglia, B., Mencacci, N.E., Lubbe, S.J., and Nardocci, N.
- Subjects
bcs - Abstract
Background: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia. \ud Objective: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged less than 18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease. \ud Methods: Whole-exome sequencing or customized gene panels were used to screen a cohort of sixty-five patients who had previously tested negative for all other known dystonia-associated genes.\ud Results: We identified fourteen patients (21.5%) carrying KMT2B variants, of which one was classified as a Variant of Unknown Significance (VUS). We also identified two additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudo-cranial generalization. Eight patients underwent pallidal Deep Brain Stimulation with a median decrease of BFMDRS-M score of 38.5% in the long term. We also report four asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance. \ud Conclusions: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to Deep Brain Stimulation is characteristic of DYT-KMT2B dystonia.
- Published
- 2019
5. Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study
- Author
-
Carecchio, M., Invernizzi, F., Gonzalez-Latapi, P., Panteghini, C., Zorzi, Gianni, Romito, Luigi Michele Antonio, Leuzzi, V., Galosi, S., Reale, C., Zibordi, Federica, Joseph, A. P., Topf, M., Piano, Carla, Bentivoglio, Anna Rita, Girotti, Francesco, Morana, P., Morana, B., Kurian, M. A., Garavaglia, B., Mencacci, N. E., Lubbe, S. J., Nardocci, N., Romito L., Zibordi F., Piano C., Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Carecchio, M., Invernizzi, F., Gonzalez-Latapi, P., Panteghini, C., Zorzi, Gianni, Romito, Luigi Michele Antonio, Leuzzi, V., Galosi, S., Reale, C., Zibordi, Federica, Joseph, A. P., Topf, M., Piano, Carla, Bentivoglio, Anna Rita, Girotti, Francesco, Morana, P., Morana, B., Kurian, M. A., Garavaglia, B., Mencacci, N. E., Lubbe, S. J., Nardocci, N., Romito L., Zibordi F., Piano C., and Bentivoglio A. R. (ORCID:0000-0002-9663-095X)
- Abstract
Background: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia. Objective: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged <18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease. Methods: Whole-exome sequencing or customized gene panels were used to screen a cohort of 65 patients who had previously tested negative for all other known dystonia-associated genes. Results: We identified 14 patients (21.5%) carrying KMT2B variants, of which 1 was classified as a variant of unknown significance. We also identified 2 additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudocranial generalization. Eight patients underwent pallidal DBS with a median decrease of Burke-Fahn-Marsden Dystonia Rating Scale-Motor score of 38.5% in the long term. We also report on 4 asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance. Conclusions: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome, often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to DBS is characteristic of DYT-KMT2B dystonia. © 2019 International Parkinson and Movement Disorder Society.
- Published
- 2019
6. Encephalopathies with intracranial calcification in children: clinical and genetic characterization
- Author
-
Tonduti D, Panteghini C, Pichiecchio A, Decio A, Carecchio M, Reale C, Moroni I, Nardocci N, Campistol-Plana J, Garcia-Cazorla A, Pérez-Dueñas B, Cerebral Calcification International Study Group, Chiapparini L, Garavaglia B, and Orcesi S
- Subjects
Cerebral calcification ,Leukodystrophy ,Aicardi-Goutières syndrome ,Next generation sequencing - Abstract
BACKGROUND: We present a group of patients affected by a paediatric onset genetic encephalopathy with cerebral calcification of unknown aetiology studied with Next Generation Sequencing (NGS) genetic analyses. METHODS: We collected all clinical and radiological data. DNA samples were tested by means of a customized gene panel including fifty-nine genes associated with known genetic diseases with cerebral calcification. RESULTS: We collected a series of fifty patients. All patients displayed complex and heterogeneous phenotypes mostly including developmental delay and pyramidal signs and less frequently movement disorder and epilepsy. Signs of cerebellar and peripheral nervous system involvement were occasionally present. The most frequent MRI abnormality, beside calcification, was the presence of white matter alterations; calcification was localized in basal ganglia and cerebral white matter in the majority of cases. Sixteen out of fifty patients tested positive for mutations in one of the fifty-nine genes analyzed. In fourteen cases the analyses led to a definite genetic diagnosis while results were controversial in the remaining two. CONCLUSIONS: Genetic encephalopathies with cerebral calcification are usually associated to complex phenotypes. In our series, a molecular diagnosis was achieved in 32% of cases, suggesting that the molecular bases of a large number of disorders are still to be elucidated. Our results confirm that cerebral calcification is a good criterion to collect homogeneous groups of patients to be studied by exome or whole genome sequencing; only a very close collaboration between clinicians, neuroradiologists and geneticists can provide better results from these new generation molecular techniques.
- Published
- 2018
7. A PDE10A de novo mutation causes childhood-onset chorea with diurnal fluctuations
- Author
-
Esposito, S., Carecchio, M., Tonduti, D., Saletti, V., Panteghini, C., Chiapparini, L., Zorzi, G., Pantaleoni, C., Garavaglia, B., Krainc, D., Lubbe, S. J., Nardocci, N., and Mencacci, N. E.
- Subjects
Male ,Phosphoric Diester Hydrolases ,Chorea ,Mutation ,Brain ,Humans ,Child ,Preschool ,Chronobiology Disorders ,Child, Preschool ,Magnetic Resonance Imaging - Published
- 2017
8. ADCY5-related movement disorders: Frequency, disease course and phenotypic variability in a cohort of paediatric patients
- Author
-
Carecchio, M. Mencacci, N.E. Iodice, A. Pons, R. Panteghini, C. Zorzi, G. Zibordi, F. Bonakis, A. Dinopoulos, A. Jankovic, J. Stefanis, L. Bhatia, K.P. Monti, V. R'Bibo, L. Veneziano, L. Garavaglia, B. Fusco, C. Wood, N. Stamelou, M. Nardocci, N.
- Abstract
Introduction ADCY5 mutations have been recently identified as an important cause of early-onset hyperkinetic movement disorders. The phenotypic spectrum associated with mutations in this gene is expanding. However, the ADCY5 mutational frequency in cohorts of paediatric patients with hyperkinetic movement disorders has not been evaluated. Methods We performed a screening of the entire ADCY5 coding sequence in 44 unrelated subjects with genetically undiagnosed childhood-onset hyperkinetic movement disorders, featuring chorea alone or in combination with myoclonus and dystonia. All patients had normal CSF analysis and brain imaging and were regularly followed-up in tertiary centers for paediatric movement disorders. Results We identified five unrelated subjects with ADCY5 mutations (11% of the cohort). Three carried the p. R418W mutation, one the p. R418Q and one the p. R418G mutation. Mutations arose de novo in four cases, while one patient inherited the mutation from his similarly affected father. All patients had delayed motor and/or language milestones with or without axial hypotonia and showed generalized chorea and dystonia, with prominent myoclonic jerks in one case. Episodic exacerbations of the baseline movement disorder were observed in most cases, being the first disease manifestation in two patients. The disease course was variable, from stability to spontaneous improvement during adolescence. Conclusion Mutations in ADCY5 are responsible for a hyperkinetic movement disorder that can be preceded by episodic attacks before the movement disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral palsy. A residual degree of neck hypotonia and a myopathy-like facial appearance are frequently observed in patients with ADCY5 mutations. © 2017 The Authors
- Published
- 2017
9. Molecular subtyping of human and food-environmental Listeria monocytogenes isolates by PFGE in northern Italy (2012-2014)
- Author
-
Amato, E., Panteghini, C., Filipello, Virginia, Gori, M., Huedo, P., Tilola, M., Lomonaco, Sara, Losio, N. M., and Pontello, M.
- Published
- 2015
10. Clinical, radiological and possible pathological overlap of cystic leukoencephalopathy without megalencephaly and Aicardi-Goutieres syndrome
- Author
-
Tonduti, D., Orcesi, S., Jenkinson, E.M., Dorboz, I., Renaldo, F., Panteghini, C., Rice, G.I., Henneke, M., Livingston, J.H., Elmaleh, M., Burglen, L., Willemsen, M.A.A.P., Chiapparini, L., Garavaglia, B., Rodriguez, D., Boespflug-Tanguy, O., Moroni, I., Crow, Y.J., Tonduti, D., Orcesi, S., Jenkinson, E.M., Dorboz, I., Renaldo, F., Panteghini, C., Rice, G.I., Henneke, M., Livingston, J.H., Elmaleh, M., Burglen, L., Willemsen, M.A.A.P., Chiapparini, L., Garavaglia, B., Rodriguez, D., Boespflug-Tanguy, O., Moroni, I., and Crow, Y.J.
- Abstract
Item does not contain fulltext, 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-Goutieres 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.
- Published
- 2016
11. 142 Cross infection of Pseudomonas aeruginosa (PA) among children under 24 months of age
- Author
-
Bassani, L., primary, Colombrita, D., additional, Panteghini, C., additional, Pavoni, E., additional, Caruso, A., additional, Padoan, R., additional, Bertasi, B., additional, Timpano, S., additional, Rodella, E., additional, and Zini, A., additional
- Published
- 2013
- Full Text
- View/download PDF
12. Screening and selection of lactic acid bacteria from calves for designing a species-specific probiotic supplement
- Author
-
Ripamonti, B., primary, Rebucci, R., additional, Stella, S., additional, Baldi, A., additional, Savoini, G., additional, Bersani, C., additional, Bertasi, B., additional, Panteghini, C., additional, and Cantoni, C., additional
- Published
- 2007
- Full Text
- View/download PDF
13. Parkinsonism in children: Clinical and etiological characterization from a tertiary referral center
- Author
-
Carecchio, M., Cavallera, V., Giovanna Zorzi, Zibordi, F., Reale, C., Panteghini, C., Monti, V., Gellera, C., Garavaglia, B., and Nardocci, N.
14. The relevance of movement disorders gene panels in clinical practice: How many patients are we sorting out?
- Author
-
Barzaghi, C., Panteghini, C., Carecchio, M., Legati, A., Monti, V., Chiara Reale, Invernizzi, F., and Garavaglia, B.
15. PFGE and automated riboprinting methods for molecular characterization of Pseudomonas fluorescens isolates involved in the 'blue-mozzarella' event,Caratterizzazione molecolare mediante elettroforesi in campo pulsato (PFGE) e riboprinting di isolati di Pseudomonas fluorescens a seguito dell'evento 'mozzarelle blu'
- Author
-
Nogarol, C., Panteghini, C., Gallina, S., Daminelli, P., Favretti, M., Stefano Bilei, Scuota, S., Caligiuri, V., Addante, N., Piraino, C., Decastelli, L., and Bertasi, B.
16. Neurodevelopmental disorder and parkinsonism in a patient with WDR45 variant: a long-term outcome
- Author
-
Manti, F., Nardecchia, F., Serena Galosi, Panteghini, C., Garavaglia, B., and Leuzzi, V.
17. Primary familial brain calcifications: Results from a monocentric study and a novel XPR1 mutation
- Author
-
Magistrelli, L., Carecchio, M., Panteghini, C., Barbara Garavaglia, Cantello, R., and Comi, C.
18. Frequency and Phenoptypic Spectrum of KMT2B Mutations in Childhood-Onset Dystonia: Results from a Single-Centre Cohort Study
- Author
-
Carecchio, M., Zorzi, G., Invernizzi, F., Panteghini, C., Luigi Romito, Zibordi, F., Leuzzi, V., Galosi, S., Morana, P., Morana, B., Piano, C., Bentivoglio, A., Reale, C., Girotti, F., Topf, M., Joseph, A., Kurian, M., Lubbe, S., Garavaglia, B., Mencacci, N., and Nardocci, N.
19. Telethon Network of Genetic Biobanks: a key service for diagnosis and research on rare diseases
- Author
-
Mirella, Filocamo, Chiara, Baldo, Stefano, Goldwurm, Renieri, Alessandra, Corrado, Angelini, Maurizio, Moggio, Marina, Mora, Giuseppe, Merla, Luisa, Politano, Barbara, Garavaglia, Lorena, Casareto, Francesca, Bricarelli, Telethon Network of Genetic Biobanks Staff, Corsolini, F, Galotto, S, Mazzotti, R, Stroppiana, G, Castagnetta, M, Mogni, M, Viotti, V, Bonetti, A, Felici, F, Natuzzi, F, Amabile, S, Frullanti, E, Meloni, I, Fanin, M, Nascimbeni, A, Pegoraro, E, Peterle, E, Napoli, L, Ripolone, M, Sciacco, M, Violano, R, Canioni, E, Gibertini, S, Saredi, S, Zanotti, S, Fusco, C, Micale, L, Pellico, Mt, Zelante, L, D'Ambrosio, P, Picillo, E, Taglia, A, Barzaghi, C, Panteghini, C, Valletta, L., Filocamo, M, Baldo, C, Goldwurm, S, Renieri, A, Angelini, C, Moggio, M, Mora, M, Merla, G, Politano, Luisa, Garavaglia, B, Casareto, L, Bricarelli, F. D., Politano, L, Bricarelli, F, and Gibertini, S
- Subjects
Biobanking ,Service (systems architecture) ,Databases, Factual ,Process (engineering) ,media_common.quotation_subject ,Biospecimens ,Translational research ,Biobanking, Networking, Biological resources centre, IT infrastructure, Biological material, Biospecimens, Cryopreservation, Rare diseases, Patients’ associations ,Biology ,Critical mass (sociodynamics) ,Biospecimen ,Networking ,Rare Diseases ,Rare Disease ,Biological Specimen Bank ,Humans ,Quality (business) ,Genetics(clinical) ,Pharmacology (medical) ,Genetic Network ,Genetics (clinical) ,Biological Specimen Banks ,media_common ,Biobank ,Cryopreservation ,Medicine(all) ,Patients’ associations ,business.industry ,Research ,Medicine (all) ,General Medicine ,Data science ,Biological resources centre ,IT infrastructure ,Identification (information) ,Patients' association ,Biological material ,Information technology management ,business ,Human - Abstract
Several examples have always illustrated how access to large numbers of biospecimens and associated data plays a pivotal role in the identification of disease genes and the development of pharmaceuticals. Hence, allowing researchers to access to significant numbers of quality samples and data, genetic biobanks are a powerful tool in basic, translational and clinical research into rare diseases. Recently demand for well-annotated and properly-preserved specimens is growing at a high rate, and is expected to grow for years to come. The best effective solution to this issue is to enhance the potentialities of well-managed biobanks by building a network.Here we report a 5-year experience of the Telethon Network of Genetic Biobanks (TNGB), a non-profit association of Italian repositories created in 2008 to form a virtually unique catalogue of biospecimens and associated data, which presently lists more than 750 rare genetic defects. The process of TNGB harmonisation has been mainly achieved through the adoption of a unique, centrally coordinated, IT infrastructure, which has enabled (i) standardisation of all the TNGB procedures and activities; (ii) creation of an updated TNGB online catalogue, based on minimal data set and controlled terminologies; (iii) sample access policy managed via a shared request control panel at web portal. TNGB has been engaged in disseminating information on its services into both scientific/biomedical - national and international - contexts, as well as associations of patients and families. Indeed, during the last 5-years national and international scientists extensively used the TNGB with different purposes resulting in more than 250 scientific publications. In addition, since its inception the TNGB is an associated member of the Biobanking and Biomolecular Resources Research Infrastructure and recently joined the EuroBioBank network. Moreover, the involvement of patients and families, leading to the formalization of various agreements between TNGB and Patients' Associations, has demonstrated how promoting Biobank services can be instrumental in gaining a critical mass of samples essential for research, as well as, raising awareness, trust and interest of the general public in Biobanks. This article focuses on some fundamental aspects of networking and demonstrates how the translational research benefits from a sustained infrastructure. © 2013 Filocamo et al.; licensee BioMed Central Ltd.
- Full Text
- View/download PDF
20. Cerebrospinal fluid neuropathological biomarkers in beta-propeller protein-associated neurodegeneration, with complicated parkinsonian phenotype
- Author
-
Roberta Bonomo, Antonio E. Elia, Roberto Cilia, Luigi M. Romito, Nico Golfrè Andreasi, Grazia Devigili, Salvatore Bonvegna, Giulia Straccia, Barbara Garavaglia, Celeste Panteghini, Roberto Eleopra, Bonomo, R, Elia, A, Cilia, R, Romito, L, Golfrè Andreasi, N, Devigili, G, Bonvegna, S, Straccia, G, Garavaglia, B, Panteghini, C, and Eleopra, R
- Subjects
Phenotype ,Neurology ,BPAN ,WDR45 ,Neuroaxonal Dystrophies ,Humans ,Neurology (clinical) ,Biomarker ,Geriatrics and Gerontology ,Iron Metabolism Disorders ,Beta-propeller protein-associated neurodegeneration ,Biomarkers ,Neuropathology - Published
- 2022
21. Harmful Iron-Calcium Relationship in Pantothenate kinase Associated Neurodegeneration
- Author
-
Stefano Taverna, Anna Cozzi, Luisa Chiapparini, Chiara Paolizzi, Ivano Di Meo, Marzia Raimondi, Alicia Rubio, Celeste Panteghini, Sonia Levi, Valeria Tiranti, Miryam Carecchio, Maddalena Ripamonti, Giuseppe De Palma, Paolo Santambrogio, Santambrogio, P., Ripamonti, M., Paolizzi, C., Panteghini, C., Carecchio, M., Chiapparini, L., Raimondi, M., Rubio, A., Di Meo, I., Cozzi, A., Taverna, S., De Palma, G., Tiranti, V., and Levi, S.
- Subjects
IPSC (induced pluripotent stem cells) ,Male ,Cytoplasm ,Mass Spectrometry ,lcsh:Chemistry ,Cohort Studies ,Homeostasis ,PKAN (pantothenate kinase-associated neurodegeneration) ,Child ,lcsh:QH301-705.5 ,Tomography ,Spectroscopy ,Neurons ,Microscopy ,Calpain ,Chemistry ,Neurodegeneration ,Brain ,General Medicine ,Magnetic Resonance Imaging ,Mitochondria ,X-Ray Computed ,Computer Science Applications ,Cell biology ,Phosphotransferases (Alcohol Group Acceptor) ,Child, Preschool ,Female ,Adolescent ,Calcium ,Iron ,NBIA (neurodegeneration with brain iron accumulation) ,Humans ,Induced Pluripotent Stem Cells ,Infant ,Microscopy, Electron ,Pantothenate Kinase-Associated Neurodegeneration ,Tomography, X-Ray Computed ,Young Adult ,chemistry.chemical_element ,Electron ,Article ,Catalysis ,Pantothenate kinase-associated neurodegeneration ,Inorganic Chemistry ,Glutamatergic ,Calcium imaging ,medicine ,Physical and Theoretical Chemistry ,Preschool ,Molecular Biology ,Calcium metabolism ,Organic Chemistry ,medicine.disease ,PANK2 ,lcsh:Biology (General) ,lcsh:QD1-999 ,Calcification - Abstract
Pantothenate Kinase-associated Neurodegeneration (PKAN) belongs to a wide spectrum of diseases characterized by brain iron accumulation and extrapyramidal motor signs. PKAN is caused by mutations in PANK2, encoding the mitochondrial pantothenate kinase 2, which is the first enzyme of the biosynthesis of Coenzyme A. We established and characterized glutamatergic neurons starting from previously developed PKAN Induced Pluripotent Stem Cells (iPSCs). Results obtained by inductively coupled plasma mass spectrometry indicated a higher amount of total cellular iron in PKAN glutamatergic neurons with respect to controls. PKAN glutamatergic neurons, analyzed by electron microscopy, exhibited electron dense aggregates in mitochondria that were identified as granules containing calcium phosphate. Calcium homeostasis resulted compromised in neurons, as verified by monitoring the activity of calcium-dependent enzyme calpain1, calcium imaging and voltage dependent calcium currents. Notably, the presence of calcification in the internal globus pallidus was confirmed in seven out of 15 genetically defined PKAN patients for whom brain CT scan was available. Moreover, we observed a higher prevalence of brain calcification in females. Our data prove that high amount of iron coexists with an impairment of cytosolic calcium in PKAN glutamatergic neurons, indicating both, iron and calcium dys-homeostasis, as actors in pathogenesis of the disease.
- Published
- 2020
22. Causative Role of the SLC6A1 p.Asp451Gly Variant in a Patient with Combined Dystonia and Neurodevelopmental Disorder.
- Author
-
Romito LM, Colucci F, Leta V, Panteghini C, Telese R, Tolva G, Villa R, Elia AE, Eleopra R, Peron A, Garavaglia B, and Iascone M
- Published
- 2024
- Full Text
- View/download PDF
23. Aceruloplasminemia: Unique Clinical and MRI Findings in a Patient with a Novel Frameshift Mutation.
- Author
-
Colucci F, Barca S, Cilia R, De Franco V, Elia AE, Golfrè Andreasi N, Romito L, Telese R, Braccia A, Leta V, Grisoli M, Panteghini C, Garavaglia B, Devigili G, and Eleopra R
- Subjects
- Humans, Iron Metabolism Disorders genetics, Iron Metabolism Disorders diagnosis, Iron Metabolism Disorders diagnostic imaging, Iron Metabolism Disorders pathology, Male, Female, Frameshift Mutation, Magnetic Resonance Imaging, Ceruloplasmin deficiency, Ceruloplasmin genetics, Ceruloplasmin metabolism, Neurodegenerative Diseases genetics, Neurodegenerative Diseases diagnostic imaging, Neurodegenerative Diseases diagnosis, Neurodegenerative Diseases pathology
- Published
- 2024
- Full Text
- View/download PDF
24. Long-Term Globus Pallidus Internus Deep Brain Stimulation in Pediatric Non-Degenerative Dystonia: A Cohort Study and a Meta-Analysis.
- Author
-
Duga V, Giossi R, Romito LM, Stanziano M, Levi V, Panteghini C, Zorzi G, and Nardocci N
- Subjects
- Child, Female, Humans, Male, Cohort Studies, Dystonia therapy, Dystonic Disorders therapy, Dystonic Disorders physiopathology, Retrospective Studies, Treatment Outcome, Deep Brain Stimulation methods, Globus Pallidus
- Abstract
Background: The evidence in the effectiveness of deep brain stimulation in children with medication-refractory non-degenerative monogenic dystonia is heterogeneous and long-term results are sparse., Objectives: The objective is to describe long-term outcomes in a single-center cohort and compare our results with a meta-analysis cohort form literature., Methods: We performed a retrospective single-center cohort study including consecutive pediatric patients with non-degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual-patient data meta-analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M) score., Results: The clinical cohort included 25 patients with a mean study follow-up of 11.4 years. The meta-analysis cohort included 224 patients with a mean follow-up of 3 years. Overall, the BFMDRS-M mean improvements at 1 year and at last follow-up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta-analysis cohort, respectively. TOR1A-dystonia showed the greatest and most stable BFMDRS-M improvement in both cohorts at 1 year and at last follow-up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta-analysis cohort), followed by SGCE-dystonia (63% and 63.9% in the meta-analysis cohort). THAP1-dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta-analysis cohort) and KMT2B-dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta-analysis cohort) showed a less pronounced or sustained response., Conclusion: Globus pallidus deep brain stimulation long-term treatment seems effective with a possible gene-specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
- Published
- 2024
- Full Text
- View/download PDF
25. Illustration of the long-term efficacy of pallidal deep brain stimulation in a patient with PKAN dystonia.
- Author
-
Romito LM, Colucci F, Zorzi G, Garavaglia B, Kaymak A, Mazzoni A, Panteghini C, Golfrè Andreasi N, Rinaldo S, Levi V, Carecchio M, and Eleopra R
- Subjects
- Humans, Dystonia therapy, Treatment Outcome, Deep Brain Stimulation methods, Dystonic Disorders therapy, Dystonic Disorders physiopathology, Globus Pallidus
- Abstract
Competing Interests: Declaration of competing interest All authors report no competing interests.
- Published
- 2024
- Full Text
- View/download PDF
26. Reply to: "Heterogeneous Phenotypic Evolution in ANO3-Related Dystonia Due to the Recurrent p.Glu510Lys Variant".
- Author
-
Romito LM, Leta V, Garavaglia B, Panteghini C, Zorzi G, Elia AE, Colucci F, Carecchio M, and Eleopra R
- Subjects
- Humans, Anoctamins genetics, Mutation genetics, Dystonia genetics, Dystonic Disorders genetics, Myoclonus
- Published
- 2024
- Full Text
- View/download PDF
27. Dominant VPS16 Pathogenic Variants: Not Only Isolated Dystonia.
- Author
-
Monfrini E, Avanzino L, Palermo G, Bonato G, Brescia G, Ceravolo R, Cantarella G, Mandich P, Prokisch H, Storm Van's Gravesande K, Straccia G, Elia A, Reale C, Panteghini C, Zorzi G, Eleopra R, Erro R, Carecchio M, Garavaglia B, Zech M, Romito L, and Di Fonzo A
- Subjects
- Humans, Vesicular Transport Proteins, Dystonia diagnosis, Gait Disorders, Neurologic, Deep Brain Stimulation methods, Parkinson Disease, Dystonic Disorders diagnosis
- Abstract
Background: VPS16 pathogenic variants have been recently associated with inherited dystonia. Most patients affected by dominant VPS16-related disease display early-onset isolated dystonia with prominent oromandibular, bulbar, cervical, and upper limb involvement, followed by slowly progressive generalization., Cases: We describe six newly reported dystonic patients carrying VPS16 mutations displaying unusual phenotypic features in addition to dystonia, such as myoclonus, choreoathetosis, pharyngospasm and freezing of gait. Response to bilateral Globus Pallidus Internus Deep Brain Stimulation (GPi-DBS) is reported in three of them, associated with significant improvement of dystonia but only minor effect on other hyperkinetic movements. Moreover, five novel pathogenic/likely pathogenic variants are described., Conclusions: This case collection expands the genetic and clinical spectrum of VPS16-related disease, prompting movement disorder specialists to suspect mutations of this gene not only in patients with isolated dystonia., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
- Published
- 2024
- Full Text
- View/download PDF
28. ANO3 as a Cause of Early-Onset Chorea Combined with Dystonia: Illustration of Phenotypic Evolution.
- Author
-
Romito LM, Leta V, Garavaglia B, Panteghini C, Zorzi G, Elia AE, Colucci F, Carecchio M, and Eleopra R
- Subjects
- Humans, Mutation, Anoctamins genetics, Dystonia complications, Chorea complications, Chorea genetics, Dystonic Disorders complications, Dystonic Disorders genetics
- Published
- 2024
- Full Text
- View/download PDF
29. Harmonizing Genetic Testing for Parkinson's Disease: Results of the PARKNET Multicentric Study.
- Author
-
Di Fonzo A, Percetti M, Monfrini E, Palmieri I, Albanese A, Avenali M, Bartoletti-Stella A, Blandini F, Brescia G, Calandra-Buonaura G, Campopiano R, Capellari S, Colangelo I, Comi GP, Cuconato G, Ferese R, Galandra C, Gambardella S, Garavaglia B, Gaudio A, Giardina E, Invernizzi F, Mandich P, Mineri R, Panteghini C, Reale C, Trevisan L, Zampatti S, Cortelli P, and Valente EM
- Subjects
- Humans, Middle Aged, Adult, Retrospective Studies, Mutation, Genetic Testing, Age of Onset, Parkinson Disease diagnosis, Parkinson Disease genetics
- Abstract
Background and Objective: Early-onset Parkinson's disease (EOPD) commonly recognizes a genetic basis; thus, patients with EOPD are often addressed to diagnostic testing based on next-generation sequencing (NGS) of PD-associated multigene panels. However, NGS interpretation can be challenging in a diagnostic setting, and few studies have addressed this issue so far., Methods: We retrospectively collected data from 648 patients with PD with age at onset younger than 55 years who underwent NGS of a minimal shared panel of 15 PD-related genes, as well as PD-multiplex ligation-dependent probe amplification in eight Italian diagnostic laboratories. Data included a minimal clinical dataset, the complete list of variants included in the diagnostic report, and final interpretation (positive/negative/inconclusive). Patients were further stratified based on age at onset ≤40 years (very EOPD, n = 157). All variants were reclassified according to the latest American College of Medical Genetics and Genomics criteria. For classification purposes, PD-associated GBA1 variants were considered diagnostic., Results: In 186 of 648 (29%) patients, the diagnostic report listed at least one variant, and the outcome was considered diagnostic (positive) in 105 (16%). After reanalysis, diagnosis changed in 18 of 186 (10%) patients, with 5 shifting from inconclusive to positive and 13 former positive being reclassified as inconclusive. A definite diagnosis was eventually reached in 97 (15%) patients, of whom the majority carried GBA1 variants or, less frequently, biallelic PRKN variants. In 89 (14%) cases, the genetic report was inconclusive., Conclusions: This study attempts to harmonize reporting of PD genetic testing across several diagnostic labs and highlights current difficulties in interpreting genetic variants emerging from NGS-multigene panels, with relevant implications for counseling. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
- Published
- 2023
- Full Text
- View/download PDF
30. Sex distribution and classification of GBA1 variants in an Italian cohort of Parkinson's disease patients analyzed over the last seventeen years.
- Author
-
Panteghini C, Reale C, Colangelo I, Suerz M, Catania A, Garavaglia B, and Invernizzi F
- Subjects
- Female, Humans, Male, Heterozygote, Italy, Mutation genetics, Sex Factors, Glucosylceramidase genetics, Parkinson Disease genetics
- Abstract
Introduction: Heterozygous GBA1 variants are among the most frequent genetic risk factors for Parkinson's disease (PD). Male sex is a risk factor in the development of PD but the sex prevalence of GBA1 carriers in PD patients remains debatable. Molecular analysis of the GBA1 gene is complicated by the presence of a highly homologous pseudogene GBAP1., Method: Starting from 2006, we screened GBA1 gene in a large cohort of 1762 PD patients through different techniques developed over the years. Identified variants were classified employing the GBA1-PD browser and compared on the basis of frequency and sex distribution., Results: Within a group of 684 patients (40.2% Males -M-) analyzed with RFLP technique looking for the two most common GBA1 mutations L444P and N370S, 29 resulted positive (4.23%). Out of 537 patients (67.4% M) analyzed with PCR that amplifies the portion of the gene between exon 8 and exon 11, we found 53 positive carriers (9.87%). Out of 424 patients (60.8% M) analyzed with NGS custom gene panel with allele-specific PCR, 50 resulted positive (11.79%). Since 2022, we also analyzed 117 patients (56.4% M) with long PCR sequenced with NGS, identifying 17 positive samples (14.52%)., Conclusion: In our study, we highlight that screening the entire GBA1 gene with specific techniques increases the diagnostic rate. Regarding variants distribution, males have shown a higher frequency of the severe variants and complex alleles, whereas mild variants are equally distributed in both sexes and risk variants are more frequent in females especially the T369 M., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
31. A novel GNAL pathogenic variant leading to generalized dystonia: Immediate and sustained response to globus pallidus internus deep brain stimulation.
- Author
-
Romito LM, Paio F, Andreasi NG, Panteghini C, Rinaldo S, Kaymak A, Mazzoni A, Colucci F, Levi V, Messina G, Garavaglia B, and Eleopra R
- Subjects
- Humans, Globus Pallidus physiology, Treatment Outcome, Deep Brain Stimulation, Dystonia therapy, Dystonic Disorders genetics, Dystonic Disorders therapy
- Abstract
Competing Interests: Declaration of competing interest All authors report no competing interests.
- Published
- 2023
- Full Text
- View/download PDF
32. Genetics, sex, and gender.
- Author
-
Reale C, Invernizzi F, Panteghini C, and Garavaglia B
- Subjects
- Male, Humans, Female, Sex Factors, Precision Medicine, Sex Characteristics, Gender Identity, Aging
- Abstract
This review aims to give an overview of what has been discovered so far and what still needs to be analyzed about how sex and gender affect the disease development. These two terms are often confused and indifferently used. In principle, the term "sex" refers to biological differences between males and females, specifically reproductive organs and their functions, while the term "gender" refers to the social context in which people live and which contributes to a subjective sexual identity, masculine or feminine. This dichotomy, however, is not so rigid and both sex and gender influence different aspects of human health, such as brain, health and aging and drug treatment and pharmacokinetics. In particular, we want to focus on genetic differences between men and women: indeed, the expression of the genes mapped on X chromosome or Y chromosome and all epigenetic interactions affect the diseases development. Finally, we will briefly outline sex and gender differences in clinical manifestations of three neurological diseases: Alzheimer's disease, Parkinson's disease, and obsessive compulsive disorder. In the era of personalized medicine, we must not forget the importance of gender medicine to promote personalized care for any kind of patients., (© 2021 Wiley Periodicals LLC.)
- Published
- 2023
- Full Text
- View/download PDF
33. Two Cases of TMEM151A -Associated Paroxysmal Dyskinesia in a Single-Center Series of PRRT2-Negative Patients.
- Author
-
Satolli S, Invernizzi F, Danti FR, Reale C, Panteghini C, Nardocci N, Garavaglia B, and Zorzi G
- Published
- 2023
- Full Text
- View/download PDF
34. Cerebrospinal fluid neuropathological biomarkers in beta-propeller protein-associated neurodegeneration, with complicated parkinsonian phenotype.
- Author
-
Bonomo R, Elia AE, Cilia R, Romito LM, Golfrè Andreasi N, Devigili G, Bonvegna S, Straccia G, Garavaglia B, Panteghini C, and Eleopra R
- Subjects
- Biomarkers, Humans, Neuropathology, Phenotype, Iron Metabolism Disorders genetics, Neuroaxonal Dystrophies genetics
- Published
- 2022
- Full Text
- View/download PDF
35. Neurodevelopmental Disorder and Late-Onset Degenerative Parkinsonism in a Patient with a WDR45 Defect.
- Author
-
Manti F, Panteghini C, Garavaglia B, and Leuzzi V
- Abstract
Competing Interests: The authors declare that there are no funding sources or conflicts of interest relevant to this work.
- Published
- 2021
- Full Text
- View/download PDF
36. Parkinson's disease-dementia in trans LRP10 and GBA variants: Response to deep brain stimulation.
- Author
-
Neri M, Braccia A, Panteghini C, Garavaglia B, Gualandi F, Cavallo MA, Scerrati A, Ferlini A, and Sensi M
- Subjects
- Dementia genetics, Genetic Variation, Humans, Male, Medical Illustration, Middle Aged, Parkinson Disease genetics, Phenotype, Treatment Outcome, Deep Brain Stimulation, Dementia therapy, Glucosylceramidase genetics, LDL-Receptor Related Proteins genetics, Parkinson Disease therapy
- Abstract
We report on a patient with Parkinson's disease and dementia who underwent DBS with excellent response in motor features; the genotype is heterozygous for a novel LRP10 variant in trans with a GBA variant. He had a more severe phenotype compared to the father who only carries the LRP10 variant., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
37. Novel deep intronic mutation in PLA2G6 causing early-onset Parkinson's disease with brain iron accumulation through pseudo-exon activation.
- Author
-
Cavestro C, Panteghini C, Reale C, Nasca A, Fenu S, Salsano E, Chiapparini L, Garavaglia B, Pareyson D, Di Meo I, and Tiranti V
- Subjects
- Adult, Age of Onset, Atrophy pathology, Female, Humans, Nervous System Malformations genetics, Neuroaxonal Dystrophies genetics, Neurodegenerative Diseases genetics, Neurodegenerative Diseases pathology, Parkinson Disease diagnosis, Parkinson Disease pathology, Phenotype, Brain pathology, Group VI Phospholipases A2 genetics, Mutation genetics, Parkinson Disease genetics
- Abstract
PLA2G6 is the causative gene for a group of autosomal recessive neurodegenerative disorders known as PLA2G6-associated neurodegeneration (PLAN). We present a case with early-onset parkinsonism, ataxia, cognitive decline, cerebellar atrophy, and brain iron accumulation. Sequencing of PLA2G6 coding regions identified only a heterozygous nonsense variant, but mRNA analysis revealed the presence of an aberrant transcript isoform due to a novel deep intronic variant (c.2035-274G > A) leading to activation of an intronic pseudo-exon. These results expand the genotypic spectrum of PLAN, showing the paramount importance of detecting possible pathogenic variants in deep intronic regions in undiagnosed patients., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
38. Childhood-onset dystonia-causing KMT2B variants result in a distinctive genomic hypermethylation profile.
- Author
-
Ciolfi A, Foroutan A, Capuano A, Pedace L, Travaglini L, Pizzi S, Andreani M, Miele E, Invernizzi F, Reale C, Panteghini C, Iascone M, Niceta M, Gavrilova RH, Schultz-Rogers L, Agolini E, Bedeschi MF, Prontera P, Garibaldi M, Galosi S, Leuzzi V, Soliveri P, Olson RJ, Zorzi GS, Garavaglia BM, Tartaglia M, and Sadikovic B
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Cohort Studies, Epigenesis, Genetic, Female, Genetic Variation, Humans, Infant, Infant, Newborn, Male, Middle Aged, Mutation, Phenotype, DNA Methylation genetics, Dystonic Disorders complications, Dystonic Disorders genetics, Dystonic Disorders physiopathology, Histone-Lysine N-Methyltransferase genetics, Histone-Lysine N-Methyltransferase metabolism
- Abstract
Background: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. Heterozygous variants in lysine methyltransferase 2B (KMT2B), encoding a histone H3 methyltransferase, have been associated with a childhood-onset, progressive and complex form of dystonia (dystonia 28, DYT28). Since 2016, more than one hundred rare KMT2B variants have been reported, including frameshift, nonsense, splice site, missense and other in-frame changes, many having an uncertain clinical impact., Results: We characterize the genome-wide peripheral blood DNA methylation profiles of a cohort of 18 patients with pathogenic and unclassified KMT2B variants. We resolve the "episignature" associated with KMT2B haploinsufficiency, proving that this approach is robust in diagnosing clinically unsolved cases, properly classifying them with respect to other partially overlapping dystonic phenotypes, other rare neurodevelopmental disorders and healthy controls. Notably, defective KMT2B function in DYT28 causes a non-random DNA hypermethylation across the genome, selectively involving promoters and other regulatory regions positively controlling gene expression., Conclusions: We demonstrate a distinctive DNA hypermethylation pattern associated with DYT28, provide an epigenetic signature for this disorder enabling accurate diagnosis and reclassification of ambiguous genetic findings and suggest potential therapeutic approaches., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
39. Clinical, molecular and glycophenotype insights in SLC39A8-CDG.
- Author
-
Bonaventura E, Barone R, Sturiale L, Pasquariello R, Alessandrì MG, Pinto AM, Renieri A, Panteghini C, Garavaglia B, Cioni G, and Battini R
- Subjects
- Glycosylation, Humans, Manganese, Polysaccharides, Congenital Disorders of Glycosylation genetics, Leigh Disease
- Abstract
Background: SLC39A8, a gene located on chromosome 4q24, encodes for the manganese (Mn) transporter ZIP8 and its detrimental variants cause a type 2 congenital disorder of glycosylation (CDG). The common SLC39A8 missense variant A391T is associated with increased risk for multiple neurological and systemic disorders and with decreased serum Mn. Patients with SLC39A8-CDG present with different clinical and neuroradiological features linked to variable transferrin glycosylation profile. Galactose and Mn supplementation therapy results in the biochemical and clinical amelioration of treated patients., Results: Here, we report clinical manifestations, neuroradiological features and glycophenotypes associated with novel SLC39A8 variants (c.1048G > A; p.Gly350Arg and c.131C > G; p.Ser44Trp) in two siblings of the same Italian family. Furthermore, we describe a third patient with overlapping clinical features harbouring the homozygous missense variant A391T. The clinical phenotype of the three patients was characterized by severe developmental disability, dystonic postural pattern and dyskinesia with a more severe progression of the disease in the two affected siblings. Neuroimaging showed a Leigh syndrome-like pattern involving the basal ganglia, thalami and white matter. In the two siblings, atrophic cerebral and cerebellum changes consistent with SLC39A8-CDG were detected as well. Serum transferrin isoelectric focusing (IEF) yielded variable results with slight increase of trisialotransferrin isoforms or even normal pattern. MALDI-MS showed the presence of hypogalactosylated transferrin N-glycans, spontaneously decreasing during the disease course, only in one affected sibling. Total serum N-glycome depicted a distinct pattern for the three patients, with increased levels of undergalactosylated and undersialylated precursors of fully sialylated biantennary glycans, including the monosialo-monogalacto-biantennary species A2G1S1., Conclusions: Clinical, MRI and glycosylation features of patients are consistent with SLC39A8-CDG. We document two novel variants associated with Leigh syndrome-like disease presentation of SLC39A8-CDG. We show, for the first time, a severe neurological phenotype overlapping with that described for SLC39A8-CDG in association with the homozygous A391T missense variant. We observed a spontaneous amelioration of transferrin N-glycome, highlighting the efficacy of MS-based serum glycomics as auxiliary tool for the diagnosis and clinical management of therapy response in patients with SLC39A8-CDG. Further studies are needed to analyse more in depth the influence of SLC39A8 variants, including the common missense variant, on the expression and function of ZIP8 protein, and their impact on clinical, biochemical and neuroradiological features., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
40. THAP1 Dystonia with Globus Pallidus T2 Hypointensity: A Report of Two Cases.
- Author
-
Zorzi G, Danti FR, Reale C, Panteghini C, Invernizzi F, Moroni I, Garavaglia B, Nardocci N, and Chiapparini L
- Subjects
- Apoptosis Regulatory Proteins, DNA-Binding Proteins, Globus Pallidus, Humans, Dystonia, Dystonia Musculorum Deformans
- Published
- 2021
- Full Text
- View/download PDF
41. YY1-Related Dystonia: Clinical Aspects and Long-Term Response to Deep Brain Stimulation.
- Author
-
Zorzi G, Keller Sarmiento IJ, Danti FR, Bustos BI, Invernizzi F, Panteghini C, Reale C, Garavaglia B, Chiapparini L, Lubbe SJ, Nardocci N, and Mencacci NE
- Subjects
- Adult, Globus Pallidus, Humans, Male, Treatment Outcome, YY1 Transcription Factor, Deep Brain Stimulation, Dystonia genetics, Dystonia therapy, Dystonic Disorders genetics, Dystonic Disorders therapy
- Published
- 2021
- Full Text
- View/download PDF
42. EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia.
- Author
-
Kuipers DJS, Mandemakers W, Lu CS, Olgiati S, Breedveld GJ, Fevga C, Tadic V, Carecchio M, Osterman B, Sagi-Dain L, Wu-Chou YH, Chen CC, Chang HC, Wu SL, Yeh TH, Weng YH, Elia AE, Panteghini C, Marotta N, Pauly MG, Kühn AA, Volkmann J, Lace B, Meijer IA, Kandaswamy K, Quadri M, Garavaglia B, Lohmann K, Bauer P, Mencacci NE, Lubbe SJ, Klein C, Bertoli-Avella AM, and Bonifati V
- Subjects
- Adolescent, Adult, Age of Onset, Asian People, Brain diagnostic imaging, Child, Child, Preschool, Dystonic Disorders metabolism, Dystonic Disorders physiopathology, Female, Genome-Wide Association Study, Humans, Infant, Magnetic Resonance Imaging, Male, Middle Aged, Mutation, Missense, Pedigree, White People, Exome Sequencing, Young Adult, eIF-2 Kinase metabolism, Dystonic Disorders genetics, Fibroblasts metabolism, eIF-2 Kinase genetics
- Abstract
Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia., Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients., Results: We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) gene, segregating with early onset isolated generalized dystonia in 5 patients of a Taiwanese family. EIF2AK2 sequencing in 191 unrelated patients with unexplained dystonia yielded 2 unrelated Caucasian patients with an identical heterozygous c.388G>A, p.Gly130Arg variant, occurring de novo in one case, another patient carrying a different heterozygous variant, c.413G>C, p.Gly138Ala, and one last patient, born from consanguineous parents, carrying a third, homozygous variant c.95A>C, p.Asn32Thr. These 3 missense variants are absent from gnomAD, and are located in functional domains of the encoded protein. In 3 patients, additional neurological manifestations were present, including intellectual disability and spasticity. EIF2AK2 encodes a kinase (protein kinase R [PKR]) that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), which orchestrates the cellular stress response. Our expression studies showed abnormally enhanced activation of the cellular stress response, monitored by PKR-mediated phosphorylation of eIF2α, in fibroblasts from patients with EIF2AK2 variants. Intriguingly, PKR can also be regulated by PRKRA (protein interferon-inducible double-stranded RNA-dependent protein kinase activator A), the product of another gene causing monogenic dystonia., Interpretation: We identified EIF2AK2 variants implicated in early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. Our findings provide direct evidence for a key role of a dysfunctional eIF2α pathway in the pathogenesis of dystonia. ANN NEUROL 2021;89:485-497., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2021
- Full Text
- View/download PDF
43. Harmful Iron-Calcium Relationship in Pantothenate kinase Associated Neurodegeneration.
- Author
-
Santambrogio P, Ripamonti M, Paolizzi C, Panteghini C, Carecchio M, Chiapparini L, Raimondi M, Rubio A, Di Meo I, Cozzi A, Taverna S, De Palma G, Tiranti V, and Levi S
- Subjects
- Adolescent, Brain diagnostic imaging, Brain pathology, Calcium adverse effects, Calpain metabolism, Child, Child, Preschool, Cohort Studies, Cytoplasm physiology, Female, Homeostasis, Humans, Induced Pluripotent Stem Cells, Infant, Iron adverse effects, Magnetic Resonance Imaging, Male, Mass Spectrometry, Microscopy, Electron, Mitochondria enzymology, Mitochondria ultrastructure, Neurons physiology, Neurons ultrastructure, Pantothenate Kinase-Associated Neurodegeneration pathology, Phosphotransferases (Alcohol Group Acceptor), Tomography, X-Ray Computed, Young Adult, Calcium metabolism, Iron metabolism, Mitochondria metabolism, Neurons metabolism, Pantothenate Kinase-Associated Neurodegeneration metabolism
- Abstract
Pantothenate Kinase-associated Neurodegeneration (PKAN) belongs to a wide spectrum of diseases characterized by brain iron accumulation and extrapyramidal motor signs. PKAN is caused by mutations in PANK2, encoding the mitochondrial pantothenate kinase 2, which is the first enzyme of the biosynthesis of Coenzyme A. We established and characterized glutamatergic neurons starting from previously developed PKAN Induced Pluripotent Stem Cells (iPSCs). Results obtained by inductively coupled plasma mass spectrometry indicated a higher amount of total cellular iron in PKAN glutamatergic neurons with respect to controls. PKAN glutamatergic neurons, analyzed by electron microscopy, exhibited electron dense aggregates in mitochondria that were identified as granules containing calcium phosphate. Calcium homeostasis resulted compromised in neurons, as verified by monitoring the activity of calcium-dependent enzyme calpain1, calcium imaging and voltage dependent calcium currents. Notably, the presence of calcification in the internal globus pallidus was confirmed in seven out of 15 genetically defined PKAN patients for whom brain CT scan was available. Moreover, we observed a higher prevalence of brain calcification in females. Our data prove that high amount of iron coexists with an impairment of cytosolic calcium in PKAN glutamatergic neurons, indicating both, iron and calcium dys-homeostasis, as actors in pathogenesis of the disease.
- Published
- 2020
- Full Text
- View/download PDF
44. Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study.
- Author
-
Carecchio M, Invernizzi F, Gonzàlez-Latapi P, Panteghini C, Zorzi G, Romito L, Leuzzi V, Galosi S, Reale C, Zibordi F, Joseph AP, Topf M, Piano C, Bentivoglio AR, Girotti F, Morana P, Morana B, Kurian MA, Garavaglia B, Mencacci NE, Lubbe SJ, and Nardocci N
- Subjects
- Adolescent, Adult, Aged, Child, Cohort Studies, Deep Brain Stimulation methods, Female, Humans, Intellectual Disability genetics, Male, Middle Aged, Mutation genetics, Phenotype, Young Adult, Dystonic Disorders genetics, Histone-Lysine N-Methyltransferase genetics
- Abstract
Background: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia., Objective: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged <18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease., Methods: Whole-exome sequencing or customized gene panels were used to screen a cohort of 65 patients who had previously tested negative for all other known dystonia-associated genes., Results: We identified 14 patients (21.5%) carrying KMT2B variants, of which 1 was classified as a variant of unknown significance. We also identified 2 additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudocranial generalization. Eight patients underwent pallidal DBS with a median decrease of Burke-Fahn-Marsden Dystonia Rating Scale-Motor score of 38.5% in the long term. We also report on 4 asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance., Conclusions: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome, often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to DBS is characteristic of DYT-KMT2B dystonia. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)
- Published
- 2019
- Full Text
- View/download PDF
45. Molecular Genetics and Interferon Signature in the Italian Aicardi Goutières Syndrome Cohort: Report of 12 New Cases and Literature Review.
- Author
-
Garau J, Cavallera V, Valente M, Tonduti D, Sproviero D, Zucca S, Battaglia D, Battini R, Bertini E, Cappanera S, Chiapparini L, Crasà C, Crichiutti G, Dalla Giustina E, D'Arrigo S, De Giorgis V, De Simone M, Galli J, La Piana R, Messana T, Moroni I, Nardocci N, Panteghini C, Parazzini C, Pichiecchio A, Pini A, Ricci F, Saletti V, Salvatici E, Santorelli FM, Sartori S, Tinelli F, Uggetti C, Veneselli E, Zorzi G, Garavaglia B, Fazzi E, Orcesi S, and Cereda C
- Abstract
Aicardi-Goutières syndrome (AGS) is a genetically determined early onset encephalopathy characterized by cerebral calcification, leukodystrophy, and increased expression of interferon-stimulated genes (ISGs). Up to now, seven genes ( TREX1, RNASEH2B, RNASEH2C, RNASEH2A, ADAR1, SAMHD1, IFIH1 ) have been associated with an AGS phenotype. Next Generation Sequencing (NGS) analysis was performed on 51 AGS patients and interferon signature (IS) was investigated in 18 AGS patients and 31 healthy controls. NGS identified mutations in 48 of 51 subjects, with three patients demonstrating a typical AGS phenotype but not carrying mutations in known AGS-related genes. Five mutations, in RNASEH2B , SAMHD1 and IFIH1 gene, were not previously reported. Eleven patients were positive and seven negatives for the upregulation of interferon signaling (IS > 2.216). This work presents, for the first time, the genetic data of an Italian cohort of AGS patients, with a higher percentage of mutations in RNASEH2B and a lower frequency of mutations in TREX1 than those seen in international series. RNASEH2B mutated patients showed a prevalence of negative IS consistent with data reported in the literature. We also identified five novel pathogenic mutations that warrant further functional investigation. Exome/genome sequencing will be performed in future studies in patients without a mutation in AGS-related genes.
- Published
- 2019
- Full Text
- View/download PDF
46. Substantia Nigra Swelling and Dentate Nucleus T2 Hyperintensity May Be Early Magnetic Resonance Imaging Signs of β-Propeller Protein-Associated Neurodegeneration.
- Author
-
Russo C, Ardissone A, Freri E, Gasperini S, Moscatelli M, Zorzi G, Panteghini C, Castellotti B, Garavaglia B, Nardocci N, and Chiapparini L
- Abstract
Background and Methods: Mutations in WDR45 cause β-propeller protein-associated neurodegeneration (BPAN), a type of neurodegeneration with brain iron accumulation (NBIA). We reviewed clinical and MRI findings in 4 patients with de novo WDR45 mutations., Results: Psychomotor delay and movement disorders were present in all cases; early-onset epileptic encephalopathy was present in 3. In all cases, first MRI showed: prominent bilateral SN enlargement, bilateral dentate nuclei T2-hyperintensity, and corpus callosum thinning. Iron deposition in the SN and globus pallidus (GP) only became evident later. Diffuse cerebral atrophy was present in 3 cases., Conclusions: In this series, SN swelling and dentate nucleus T2 hyperintensity were early signs of BPAN, later followed by progressive iron deposition in the SN and GP. When clinical suspicion is raised, MRI is crucial for identifying early features suggesting this type of NBIA.
- Published
- 2018
- Full Text
- View/download PDF
47. Primary brain calcification: an international study reporting novel variants and associated phenotypes.
- Author
-
Ramos EM, Carecchio M, Lemos R, Ferreira J, Legati A, Sears RL, Hsu SC, Panteghini C, Magistrelli L, Salsano E, Esposito S, Taroni F, Richard AC, Tranchant C, Anheim M, Ayrignac X, Goizet C, Vidailhet M, Maltete D, Wallon D, Frebourg T, Pimentel L, Geschwind DH, Vanakker O, Galasko D, Fogel BL, Innes AM, Ross A, Dobyns WB, Alcantara D, O'Driscoll M, Hannequin D, Campion D, Oliveira JR, Garavaglia B, Coppola G, and Nicolas G
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Brain Diseases physiopathology, Calcinosis physiopathology, Child, Cognitive Dysfunction physiopathology, Female, Heterozygote, Humans, Male, Middle Aged, Mutation genetics, Pedigree, Phenotype, Proto-Oncogene Proteins c-sis genetics, Receptor, Platelet-Derived Growth Factor beta genetics, Receptors, G-Protein-Coupled drug effects, Receptors, Virus drug effects, Sodium-Phosphate Cotransporter Proteins, Type III genetics, Xenotropic and Polytropic Retrovirus Receptor, Young Adult, Brain Diseases genetics, Calcinosis genetics, Cognitive Dysfunction genetics, Genetic Variation genetics
- Abstract
Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic.
- Published
- 2018
- Full Text
- View/download PDF
48. The relevance of gene panels in movement disorders diagnosis: A lab perspective.
- Author
-
Reale C, Panteghini C, Carecchio M, and Garavaglia B
- Subjects
- Adult, Child, Female, Genome, Human genetics, Humans, Male, Mutation, High-Throughput Nucleotide Sequencing methods, Movement Disorders diagnosis, Movement Disorders genetics
- Abstract
Next-Generation Sequencing (NGS) is a group of new methods that allow sequencing a variable number of known genes (targeted resequencing) or even the whole human genome (whole genome sequencing-WGS) and have contributed to an exponential genetic knowledge growth, especially in rare diseases, in the past few years. Since 2015, in the Molecular Neurogenetics Unit of Neurological Institute "Carlo Besta", some gene panels have become available to screen all the known genes associated with Movement Disorders (MD) in children and adults as a diagnostic package. Over 221 patients analyzed (part of the Telethon Network of Genetic Biobanks - TNGB), pathogenic variants were found in 25 (11.31%), allowing a definitive genetic diagnosis. Among them, we found mutations in 10/114 patients with dystonia (8.8%); 10/59 patients with Parkinson's disease (16.9%); 1/25 patients with Neurodegeneration with Brain Iron Accumulation (NBIA) (4%) and 4/23 patients with neurotransmitter and biopterin metabolism synthesis defect (17.4%). Our results are in line with those published in literature; targeted resequencing does not replace Sanger sequencing totally, but its usage needs to be discussed with clinicians taking into account both the patient's clinical picture and radiological and neurophysiological data., (Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
49. SLC19A3 related disorder: Treatment implication and clinical outcome of 2 new patients.
- Author
-
Tonduti D, Invernizzi F, Panteghini C, Pinelli L, Battaglia S, Fazzi E, Zorzi G, Moroni I, Garavaglia B, Chiapparini L, and Nardocci N
- Subjects
- Adult, Brain Diseases, Metabolic, Inborn pathology, Child, Preschool, Female, Humans, Male, Necrosis, Vitamin B Complex therapeutic use, Brain Diseases, Metabolic, Inborn drug therapy, Brain Diseases, Metabolic, Inborn genetics, Membrane Transport Proteins genetics, Neostriatum pathology, Thiamine therapeutic use
- Abstract
Encephalopathies with neostriatal involvement constitute a heterogeneous group of acquired and genetically inherited conditions that include Bilateral Striatal Necrosis (BSN) and other Striatal Lesions (SL) (Tonduti et al). We describe two new patients suffering from BSN due to biallelic SLC19A3 mutations. In the first patient vitamin supplementation was started early on, resulting in the remission of the clinical picture, and an almost complete normalization of the neuroradiological findings. In the second one treatment was started late, compliance was irregular and the resulting clinical outcome was poor. The clinical outcome of our two patients confirms and further stresses the importance of the early administration of vitamin supplementation in all patients presenting with neostriatal lesions, or clear bilateral striatal necrosis. Patient 2 didn't present any additional episode of acute decompensation after the age of 20 years despite having completely stopped treatment. This suggests the existence of an age dependency of thiamin requirement in humans., (Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
50. A PDE10A de novo mutation causes childhood-onset chorea with diurnal fluctuations.
- Author
-
Esposito S, Carecchio M, Tonduti D, Saletti V, Panteghini C, Chiapparini L, Zorzi G, Pantaleoni C, Garavaglia B, Krainc D, Lubbe SJ, Nardocci N, and Mencacci NE
- Subjects
- Brain diagnostic imaging, Child, Preschool, Humans, Magnetic Resonance Imaging, Male, Chorea complications, Chorea diagnostic imaging, Chorea genetics, Chronobiology Disorders diagnostic imaging, Chronobiology Disorders etiology, Chronobiology Disorders genetics, Mutation genetics, Phosphoric Diester Hydrolases genetics
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.