Search

Your search keyword '"Marangi, Giuseppe"' showing total 389 results
Start Over Author "Marangi, Giuseppe"
389 results on '"Marangi, Giuseppe"'

1. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.

Author

Nicolas, Aude, Kenna, Kevin P, Renton, Alan E, Ticozzi, Nicola, Faghri, Faraz, Chia, Ruth, Dominov, Janice A, Kenna, Brendan J, Nalls, Mike A, Keagle, Pamela, Rivera, Alberto M, van Rheenen, Wouter, Murphy, Natalie A, van Vugt, Joke JFA, Geiger, Joshua T, Van der Spek, Rick A, Pliner, Hannah A, Shankaracharya, Smith, Bradley N, Marangi, Giuseppe, Topp, Simon D, Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D, Kenna, Aoife, ITALSGEN Consortium, Mora, Gabriele, Calvo, Andrea, Mazzini, Letizia, Riva, Nilo, Mandrioli, Jessica, Caponnetto, Claudia, Battistini, Stefania, Volanti, Paolo, La Bella, Vincenzo, Conforti, Francesca L, Borghero, Giuseppe, Messina, Sonia, Simone, Isabella L, Trojsi, Francesca, Salvi, Fabrizio, Logullo, Francesco O, D'Alfonso, Sandra, Corrado, Lucia, Capasso, Margherita, Ferrucci, Luigi, Genomic Translation for ALS Care (GTAC) Consortium, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Goldstein, David B, ALS Sequencing Consortium, Gitler, Aaron D, Harris, Tim, Myers, Richard M, NYGC ALS Consortium, Phatnani, Hemali, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C, Answer ALS Foundation, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia K, LeNail, Alex, Lima, Leandro, Fraenkel, Ernest, Svendsen, Clive N, Thompson, Leslie M, Van Eyk, Jennifer E, Berry, James D, Miller, Timothy M, Kolb, Stephen J, Cudkowicz, Merit, Baxi, Emily, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, Benatar, Michael, Taylor, J Paul, Rampersaud, Evadnie, Wu, Gang, Wuu, Joanne, SLAGEN Consortium, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P, Sorarù, Gianni, Cereda, Cristina, French ALS Consortium, Corcia, Philippe, Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, and Orrell, Richard W

Subjects
ITALSGEN Consortium, Genomic Translation for ALS Care (GTAC) Consortium, ALS Sequencing Consortium, NYGC ALS Consortium, Answer ALS Foundation, Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, SLAGEN Consortium, French ALS Consortium, Project MinE ALS Sequencing Consortium, Humans, Amyotrophic Lateral Sclerosis, Cohort Studies, Amino Acid Sequence, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Genome-Wide Association Study, Young Adult, Loss of Function Mutation, Kinesins, ALS, GWAS, KIF5A, WES, WGS, axonal transport, cargo, Brain Disorders, Genetics, Human Genome, Rare Diseases, Neurosciences, Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Neurological, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Published
2018

3. Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome.

Author

Cafiero, Concetta, Marangi, Giuseppe, Orteschi, Daniela, Ali, Marwan, Asaro, Alessia, Ponzi, Emanuela, Moncada, Alice, Ricciardi, Stefania, Murdolo, Marina, Mancano, Giorgia, Contaldo, Ilaria, Leuzzi, Vincenzo, Battaglia, Domenica, Mercuri, Eugenio, Slavotinek, Anne, and Zollino, Marcella

Subjects
Adult, Child, Child, Preschool, Chromosome Deletion, Cleft Palate, Facies, Female, Frameshift Mutation, Genetic Heterogeneity, Haploinsufficiency, Heart Defects, Congenital, High-Throughput Nucleotide Sequencing, Humans, Intellectual Disability, Male, Mediator Complex, Phenotype, Sequence Deletion
Abstract

MED13L haploinsufficiency has recently been described as responsible for syndromic intellectual disability. We planned a search for causative gene variants in seven subjects with intellectual disability and overlapping dysmorphic facial features such as bulbous nasal tip, short mouth and straight eyebrows. We found two de novo frameshift variants in MED13L, consisting in single-nucleotide deletion (c.3765delC) and duplication (c.607dupT). A de novo nonsense variant (c.4420A>T) in MED13L was detected in a further subject in the course of routine whole-exome sequencing. By analyzing the clinical data of our patients along with those recently described in the literature, we confirm that there is a common, recognizable phenotype associated with MED13L haploinsufficiency, which includes intellectual disability and a distinctive facial appearance. Congenital heart diseases are found in some subjects with various degree of severity. Our observation of cleft palate, ataxia, epilepsy and childhood leukemia observed in single cases broadens the known clinical spectrum. Haploinsufficiency for MED13L should be considered in the differential diagnosis of the 1p36 microdeletion syndrome, due to overlapping dysmorphic facial features in some patients. The introduction of massive parallel-sequencing techniques into clinical practice is expected to allow for detection of other causative point variants in MED13L. Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype.

Published
2015

4. Evaluating the contribution of the gene TARDBP in Italian patients with amyotrophic lateral sclerosis

Author

Lattante, Serena, Sabatelli, Mario, Bisogni, Giulia., Marangi, Giuseppe, Doronzio, Paolo Niccolò, Martello, Francesco, Renzi, Anna Gloria, Del Giudice, Elda, Leon, Alberta, Cimbolli, Paola, Marchione, Daniela, Costantino, Umberto, Lucioli, Gabriele, Bernardo, Daniela, Meleo, Emiliana, Patanella, Agata Katia, Romano, Angela, Zollino, Marcella, Conte, Amelia, Lattante, Serena (ORCID:0000-0003-2891-0340), Sabatelli, Mario (ORCID:0000-0001-6635-4985), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Zollino, Marcella (ORCID:0000-0003-4871-9519), Lattante, Serena, Sabatelli, Mario, Bisogni, Giulia., Marangi, Giuseppe, Doronzio, Paolo Niccolò, Martello, Francesco, Renzi, Anna Gloria, Del Giudice, Elda, Leon, Alberta, Cimbolli, Paola, Marchione, Daniela, Costantino, Umberto, Lucioli, Gabriele, Bernardo, Daniela, Meleo, Emiliana, Patanella, Agata Katia, Romano, Angela, Zollino, Marcella, Conte, Amelia, Lattante, Serena (ORCID:0000-0003-2891-0340), Sabatelli, Mario (ORCID:0000-0001-6635-4985), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), and Zollino, Marcella (ORCID:0000-0003-4871-9519)

Abstract

Background and objectives: Genetic variants in the gene TARDBP, encoding TDP-43 protein, are associated with amyotrophic lateral sclerosis (ALS) in familial (fALS) and sporadic (sALS) cases. Objectives of this study were to assess the contribution of TARDBP in a large cohort of Italian ALS patients, to determine the TARDBP-associated clinical features and to look for genotype–phenotype correlation and penetrance of the mutations. Methods: A total of 1992 Italian ALS patients (193 fALS and 1799 sALS) were enrolled in this study. Sanger sequencing of TARDBP gene was performed in patients and, when available, in patients' relatives. Results: In total, 13 different rare variants were identified in 43 index cases (10 fALS and 33 sALS) with a cumulative mutational frequency of 2.2% (5.2% of fALS, 1.8% of sALS). The most prevalent variant was the p.A382T followed by the p.G294V. Cognitive impairment was detected in almost 30% of patients. While some variants, including the p.G294V and the p.G376D, were associated with restricted phenotypes, the p.A382T showed a marked clinical heterogeneity regarding age of onset, survival and association with cognitive impairment. Investigations in parents, when possible, showed that the variants were inherited from healthy carriers and never occurred de novo. Conclusions: In our cohort, TARDBP variants have a relevant frequency in Italian ALS patients and they are significantly associated with cognitive impairment. Clinical presentation is heterogeneous. Consistent genotype–phenotype correlations are limited to some mutations. A marked phenotypic variability characterizes the p.A382T variant, suggesting a multifactorial/oligogenic pathogenic mechanism.

Published
2023

5. A Genome-Wide Association Study of Myasthenia Gravis

Author

Renton, Alan E, Pliner, Hannah A, Provenzano, Carlo, Evoli, Amelia, Ricciardi, Roberta, Nalls, Michael A, Marangi, Giuseppe, Abramzon, Yevgeniya, Arepalli, Sampath, Chong, Sean, Hernandez, Dena G, Johnson, Janel O, Bartoccioni, Emanuela, Scuderi, Flavia, Maestri, Michelangelo, Gibbs, J Raphael, Errichiello, Edoardo, Chiò, Adriano, Restagno, Gabriella, Sabatelli, Mario, Macek, Mark, Scholz, Sonja W, Corse, Andrea, Chaudhry, Vinay, Benatar, Michael, Barohn, Richard J, McVey, April, Pasnoor, Mamatha, Dimachkie, Mazen M, Rowin, Julie, Kissel, John, Freimer, Miriam, Kaminski, Henry J, Sanders, Donald B, Lipscomb, Bernadette, Massey, Janice M, Chopra, Manisha, Howard, James F, Koopman, Wilma J, Nicolle, Michael W, Pascuzzi, Robert M, Pestronk, Alan, Wulf, Charlie, Florence, Julaine, Blackmore, Derrick, Soloway, Aimee, Siddiqi, Zaeem, Muppidi, Srikanth, Wolfe, Gil, Richman, David, Mezei, Michelle M, Jiwa, Theresa, Oger, Joel, Drachman, Daniel B, and Traynor, Bryan J

Subjects
Rare Diseases, Genetics, Neurosciences, Autoimmune Disease, Myasthenia Gravis, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Age of Onset, CTLA-4 Antigen, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, HLA-DQ alpha-Chains, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, United States, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ImportanceMyasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood.ObjectiveTo identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study.Design, setting, and participantsDNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody-positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication.Main outcomes and measuresWe calculated P values for association between 8,114,394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0×10(-8) was set for genome-wide significance after Bonferroni correction for multiple testing.ResultsIn the overall case-control cohort, we identified association signals at CTLA4 (rs231770; P=3.98×10(-8); odds ratio, 1.37; 95% CI, 1.25-1.49), HLA-DQA1 (rs9271871; P=1.08×10(-8); odds ratio, 2.31; 95% CI, 2.02-2.60), and TNFRSF11A (rs4263037; P=1.60×10(-9); odds ratio, 1.41; 95% CI, 1.29-1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P=1.32×10(-12); odds ratio, 1.56; 95% CI, 1.44-1.68) and the other was detected in the major histocompatibility complex on chromosome 6p21 (HLA-DQA1; rs9271871; P=7.02×10(-18); odds ratio, 4.27; 95% CI, 3.92-4.62). Association within the major histocompatibility complex region was also observed in early-onset cases (HLA-DQA1; rs601006; P=2.52×10(-11); odds ratio, 4.0; 95% CI, 3.57-4.43), although the set of single-nucleotide polymorphisms was different from that implicated among late-onset cases.Conclusions and relevanceOur genetic data provide insights into aberrant cellular mechanisms responsible for this prototypical autoimmune disorder. They also suggest that clinical trials of immunomodulatory drugs related to CTLA4 and that are already Food and Drug Administration approved as therapies for other autoimmune diseases could be considered for patients with refractory disease.

Published
2015

6. Is MED13L-related intellectual disability a recognizable syndrome?

Author

Tørring, Pernille Mathiesen, Larsen, Martin Jakob, Brasch-Andersen, Charlotte, Krogh, Lotte Nylandsted, Kibæk, Maria, Laulund, Lone, Illum, Niels, Dunkhase-Heinl, Ulrike, Wiesener, Antje, Popp, Bernt, Marangi, Giuseppe, Hjortshøj, Tina Duelund, Ek, Jakob, Vogel, Ida, Becher, Naja, Roos, Laura, Zollino, Marcella, and Fagerberg, Christina Ringmann

Published
2019
Full Text
View/download PDF

7. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Author

Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, Georgios, Appel, Stanley H., Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard, Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Allen, Andrew S., Appel, Stanley, Bedlack, Richard S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, D’Alfonso, Sandra, Corrado, Lucia, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Mazzini, Letizia, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Al Kheifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A. Nazli, Blair, Ian P., Chio, Adriano, Cooper-Knock, Jonathan, de Carvalho, Mamede, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hardiman, Orla, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Kooyman, Maarten, Landers, John, McLaughlin, Russell, Middelkoop, Bas, Mill, Jonathan, Neto, Miguel Mitne, Moisse, Mattieu, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shatunov, Aleksey, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van der Spek, Rick, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, van Vugt, Joke, Veldink, Jan, Weber, Markus, Williams, Kelly L., Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., Murphy, Natalie A., van Vugt, Joke J.F.A., Geiger, Joshua T., Van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Messina, Sonia, Simone, Isabella L., Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Wyman, Stacia K., LeNail, Alex, Van Eyk, Jennifer E., Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L.M.A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J.L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Van Eijk, Kristel R., Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Fifita, Jennifer A., Nicholson, Garth A., Esteban-Pérez, Jesús, García-Redondo, Alberto, Rogaeva, Ekaterina, Zinman, Lorne, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Van Damme, Philip, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.

Published
2018
Full Text
View/download PDF

8. Impairment of different protein domains causes variable clinical presentation within Pitt-Hopkins syndrome and suggests intragenic molecular syndromology of TCF4

Author

Bedeschi, Maria Francesca, Marangi, Giuseppe, Calvello, Maria Rosaria, Ricciardi, Stefania, Leone, Francesca Pia Chiara, Baccarin, Marco, Guerneri, Silvana, Orteschi, Daniela, Murdolo, Marina, Lattante, Serena, Frangella, Silvia, Keena, Beth, Harr, Margaret H., Zackai, Elaine, and Zollino, Marcella

Published
2017
Full Text
View/download PDF

9. Pathogenic variants in SOX11 mimicking Pitt‐Hopkins syndrome phenotype.

Author

Pasquetti, Domizia, L'Erario, Federica Francesca, Marangi, Giuseppe, Panfili, Arianna, Chiurazzi, Pietro, Sonnini, Elena, Orteschi, Daniela, Alfieri, Paolo, Morleo, Manuela, Nigro, Vincenzo, and Zollino, Marcella

Subjects
SOX transcription factors, MEDICAL genetics, HUMAN abnormalities, SYMPTOMS, FINGERNAILS, DISABILITIES
Abstract

Pitt‐Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder characterised by severe intellectual disability (ID), distinctive facial features and autonomic nervous system dysfunction, caused by TCF4 haploinsufficiency. We clinically diagnosed with PTHS a 14 6/12‐year‐old female, who had a normal status of TCF4. The pathogenic c.667del (p.Asp223MetfsTer45) variant in SOX11 was identified through whole exome sequencing (WES). SOX11 variants were initially reported to cause Coffin‐Siris syndrome (CSS), characterised by growth restriction, moderate ID, coarse face, hypertrichosis and hypoplastic nails. However, recent studies have provided evidence that they give rise to a distinct neurodevelopmental disorder. To date, SOX11 variants are associated with a variable phenotype, which has been described to resemble CSS in some cases, but never PTHS. By reviewing both clinically and genetically 32 out of 82 subjects reported in the literature with SOX11 variants, for whom detailed information are provided, we found that 7/32 (22%) had a clinical presentation overlapping PTHS. Furthermore, we made a confirmation that overall SOX11 abnormalities feature a distinctive disorder characterised by severe ID, high incidence of microcephaly and low frequency of congenital malformations. Purpose of the present report is to enhance the role of clinical genetics in assessing the individual diagnosis after WES results. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

10. Evaluating the contribution of the gene TARDBP in Italian patients with amyotrophic lateral sclerosis

Author

Lattante, Serena, primary, Sabatelli, Mario, additional, Bisogni, Giulia, additional, Marangi, Giuseppe, additional, Doronzio, Paolo Niccolò, additional, Martello, Francesco, additional, Renzi, Anna Gloria, additional, Del Giudice, Elda, additional, Leon, Alberta, additional, Cimbolli, Paola, additional, Marchione, Daniela, additional, Costantino, Umberto, additional, Lucioli, Gabriele, additional, Bernardo, Daniela, additional, Meleo, Emiliana, additional, Patanella, Agata Katia, additional, Romano, Angela, additional, Zollino, Marcella, additional, and Conte, Amelia, additional

Published
2023
Full Text
View/download PDF

11. Linear Diagnostic Procedure Elicited by Clinical Genetics and Validated by mRNA Analysis in Neuronal Ceroid Lipofuscinosis 7 Associated with a Novel Non-Canonical Splice Site Variant in MFSD8

Author

Pasquetti, Domizia, Marangi, Giuseppe, Orteschi, D., Carapelle, Marina, L'Erario, Federica Francesca, Venditti, Romina, Maietta, Sabrina, Battaglia, Domenica Immacolata, Contaldo, Ilaria, Veredice, Chiara, Zollino, Marcella, Pasquetti D., Marangi G. (ORCID:0000-0002-6898-8882), Carapelle M., L'Erario F. F., Venditti R., Maietta S., Battaglia D. I. (ORCID:0000-0003-0491-4021), Contaldo I., Veredice C., Zollino M. (ORCID:0000-0003-4871-9519), Pasquetti, Domizia, Marangi, Giuseppe, Orteschi, D., Carapelle, Marina, L'Erario, Federica Francesca, Venditti, Romina, Maietta, Sabrina, Battaglia, Domenica Immacolata, Contaldo, Ilaria, Veredice, Chiara, Zollino, Marcella, Pasquetti D., Marangi G. (ORCID:0000-0002-6898-8882), Carapelle M., L'Erario F. F., Venditti R., Maietta S., Battaglia D. I. (ORCID:0000-0003-0491-4021), Contaldo I., Veredice C., and Zollino M. (ORCID:0000-0003-4871-9519)

Abstract

Neuronal ceroid lipofuscinoses (CNL) are lysosomal storage diseases that represent the most common cause of dementia in children. To date, 13 autosomal recessive (AR) and 1 autosomal dominant (AD) gene have been characterized. Biallelic variants in MFSD8 cause CLN7 type, with nearly 50 pathogenic variants, mainly truncating and missense, reported so far. Splice site variants require functional validation. We detected a novel homozygous non-canonical splice-site variant in MFSD8 in a 5-year-old girl who presented with progressive neurocognitive impairment and microcephaly. The diagnostic procedure was elicited by clinical genetics first, and then confirmed by cDNA sequencing and brain imaging. Inferred by the common geographic origin of the parents, an autosomal recessive inheritance was hypothesized, and SNP-array was performed as the first-line genetic test. Only three AR genes lying within the observed 24 Mb regions of homozygosity were consistent with the clinical phenotype, including EXOSC9, SPATA5 and MFSD8. The cerebral and cerebellar atrophy detected in the meantime by MRI, along with the suspicion of accumulation of ceroid lipopigment in neurons, prompted us to perform targeted MFSD8 sequencing. Following the detection of a splice site variant of uncertain significance, skipping of exon 8 was demonstrated by cDNA sequencing, and the variant was redefined as pathogenic.

Published
2023

12. Analysis of STMN2 CA repeats in italian ALS patients shows no association

Author

Doronzio, Paolo Niccolo', Lattante, Serena, Marangi, Giuseppe, Martello, Francesco, Conte, A., Bisogni, G., Bernardo, D., Patanella, A. K., Meleo, Emiliana, Zollino, Marcella, Sabatelli, Mario, Doronzio P. N., Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Martello F., Meleo E., Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), Doronzio, Paolo Niccolo', Lattante, Serena, Marangi, Giuseppe, Martello, Francesco, Conte, A., Bisogni, G., Bernardo, D., Patanella, A. K., Meleo, Emiliana, Zollino, Marcella, Sabatelli, Mario, Doronzio P. N., Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Martello F., Meleo E., Zollino M. (ORCID:0000-0003-4871-9519), and Sabatelli M. (ORCID:0000-0001-6635-4985)

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by a complex interaction of genetic and environmental factors. Recently, a polymorphic intronic CA repeat in STMN2 gene has been proposed as risk factor for ALS. The presence of long/long CA genotype, especially if one allele had 24 CA, was reported to be significantly associated with the disease in a cohort of sporadic ALS patients. We tested an Italian cohort of 366 ALS patients and 353 healthy controls and we found no association between CA length and ALS risk.

Published
2023

13. CHAMP1-related disorders: pathomechanisms triggered by different genomic alterations define distinct nosological categories

Author

Amenta, Simona, Marangi, Giuseppe, Orteschi, D., Frangella, Silvia, Gurrieri, Fiorella, Paccagnella, E., Torella, A., Cappuccio, G., Musacchia, F., Mutarelli, Massimiano, Carrella, D., Vitiello, G., Parenti, Gian Paolo, Leuzzi, V., Selicorni, A., Maitz, S., Brunetti-Pierri, N., Banfi, S., Montomoli, M., Milani, Daniela, Romano, Maria Concetta, Tummolo, Aida Angela, De Brasi, D., Coppola, A., Santoro, C., Scala, M., Romano, Federica, Capra, V., Nigro, V., Zollino, Marcella, Amenta S., Marangi G. (ORCID:0000-0002-6898-8882), Frangella S., Gurrieri F. (ORCID:0000-0002-6775-5972), Mutarelli M., Parenti G., Milani D., Romano C., Tummolo A., Romano F., Zollino M. (ORCID:0000-0003-4871-9519), Amenta, Simona, Marangi, Giuseppe, Orteschi, D., Frangella, Silvia, Gurrieri, Fiorella, Paccagnella, E., Torella, A., Cappuccio, G., Musacchia, F., Mutarelli, Massimiano, Carrella, D., Vitiello, G., Parenti, Gian Paolo, Leuzzi, V., Selicorni, A., Maitz, S., Brunetti-Pierri, N., Banfi, S., Montomoli, M., Milani, Daniela, Romano, Maria Concetta, Tummolo, Aida Angela, De Brasi, D., Coppola, A., Santoro, C., Scala, M., Romano, Federica, Capra, V., Nigro, V., Zollino, Marcella, Amenta S., Marangi G. (ORCID:0000-0002-6898-8882), Frangella S., Gurrieri F. (ORCID:0000-0002-6775-5972), Mutarelli M., Parenti G., Milani D., Romano C., Tummolo A., Romano F., and Zollino M. (ORCID:0000-0003-4871-9519)

Abstract

Loss-of-function variants in CHAMP1 were recently described as cause of a neurodevelopmental disorder characterized by intellectual disability (ID), autism, and distinctive facial characteristics. By exome sequencing (ES), we identified a truncating variant in CHAMP1, c.1858A > T (p.Lys620*), in a patient who exhibited a similar phenotype of severe ID and dysmorphisms. Whether haploinsufficiency or a dominant negative effect is the underlying pathomechanism in these cases is a question that still needs to be addressed. By array-CGH, we detected a 194 kb deletion in 13q34 encompassing CHAMP1, CDC16 and UPF3, in another patient who presented with borderline neurodevelopmental impairment and with no dysmorphisms. In a further patient suffering from early onset refractory seizures, we detected by ES a missense variant in CHAMP1, c.67 G > A (p.Gly23Ser). Genomic abnormalities were all de novo in our patients. We reviewed the clinical and the genetic data of patients reported in the literature with: loss-of-function variants in CHAMP1 (total 40); chromosome 13q34 deletions ranging from 1.1 to 4 Mb (total 7) and of the unique patient with a missense variant. We could infer that loss-of-function variants in CHAMP1 cause a homogeneous phenotype with severe ID, autism spectrum disorders (ASD) and highly distinctive facial characteristics through a dominant negative effect. CHAMP1 haploinsufficiency results in borderline ID with negligible consequences on the quality of life. Missense variants give rise to a severe epileptic encephalopathy through gain-of-function mechanism, most likely. We tentatively define for the first time distinct categories among the CHAMP1-related disorder on the basis of pathomechanisms.

Published
2023

14. How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

Author

Siragusa, L., Angelico, R., Angrisani, M., Zampogna, B., Materazzo, M., Sorge, R., Giordano, Lucia, Meniconi, R., Coppola, A., Marino, A., Giraudo, G., Esposito, S., Urbani, A., De Pastena, M., Mastrapasqua, R., Garancini, M., Frontal, A., Pascal, G., Martellucc, J., Falb, F., Boscarelli, A., Bertoglio, P., Trecca, E., Galassi, L., Vento, V., Chiappini, A., Antonelli, A., Bennardo, F., Familiari, F., Giannaccare, G., Zappia, A. S., Giuliani, G., Falcone, F., Sebastiani, S., Montuori, M., Rossi, S., Sagnotta, A., Giuliani, B., Imbriani, G. C., Restaino, S., Andreani, L., Di Maria, F., Lagana, A. S., Vitiello, L., Berton, F., Virgilio, E., Palisi, M., Portigliotti, L., Calussi, M., Conti, L., Mauriello, C., Barone, Alessia Maria Addolorata, Saladino, E., Giaquinta, A., Zerb, D., Frazzetta, G., Merola, G., Chierici, A., Bini, R., Centonze, L., De Carlis, R., Ferrario, L., Giani, A., Lauterio, A., Tamini, N., Corti, Serafino, Botteri, E., Andreuccetti, J., D'Alessio, R., Cestaro, G., Clarizia, G., Spolini, A., Carboni, A. S., Benzoni, E., Galiffa, G., Perotti, B., Veroux, M., Randazzo, V., Topa, D., Pranteda, C., Contini, G., Iacusso, C., Voglino, V., Vita, P., Carrano, F. M., Ambrosio, L., Cammarata, R., Capolupo, G. T., Caputo, D., Carannante, F., Cascone, C., Esperto, F., Farolfi, T., Frasca, L., Gallo, I. F., Gibin, G., Giurazza, G., Improta, L., La Vaccara, V., Luffarelli, P., Luvero, D., Marangi, Giuseppe, Masciana, G., Mazzola, A., Mazzotta, E., Miligi, C. I., Montelione, N., Nenna, A., Orsaria, P., Papalia, R., Papalia, G. F., Parisi, F. R., Prata, F., Salzillo, R., Santini, Stefano Angelo, Sofo, F., Zampoli, A., Tanda, C., Altieri, G., Ardito, Francesco, Belia, Francesco, Bianchi, V., Biondi, Alberto, Brisinda, Giuseppe, Chiappetta, M., Ciolli, G., Ciolli, Alessandro, Ferracci, Federica, Ferri, L., Fico, V., Fiorillo, Claudio, Fransvea, Pietro, Galiandro, F., Giovinazzo, F., La Greca, Antonio, Litta, Francesco, Mele, C., Pafundi, D. P., Panettieri, Elena, Papa, Valerio, Patini, Romeo, Perrotta, Generoso, Puccioni, Caterina, Santocchi, P., Armatura, G., Olmi, S., Casoni Pattacini, G., Salgarello, S., Trompetto, M., Bombardini, C., La Rocca, R., Celentano, G., Micalef, A., Mazzella, A., Settembrini, A., Zoia, C., Degrate, L., Musumeci, Giampaolo, Palopoli, C. A. M., Montori, G., Bonati, E., Dinuzzi, V. P., Velluti, F., Balla, A., Bonasia, D. E., Coletta, D., Berardi, Giulia, Colasanti, M., Ferretti, Serena, Gasparoli, C., Mariano, Giuseppantonio, Avenia, S., Cianci, P., Cestino, L., Festa, F., Fazio, F., Ascari, F., Desio, M., Arroyo Murillo, G. A., Cereda, M., Galleano, R., David, G., Pansini, A., Gazia, C., Atzori, G., Desideri, L. F., Famularo, S., Galvanin, J., Giudici, V. M., Mangiameli, Gaetano, Mei, S., Milana, F., Pansa, A., Sacchi, Dario Marco, Testori, A., Di Carlo, Giampiero, Paratore, Mattia, Perrone, U., Vagge, A., Vigano, J., Torre, B., Scotti, M. A., Carbone, G., Cerchione, R., De Nardi, P., Gozzini, L., Ottaviani, Letizia, Senni, C., Piccin, O., Pio, L., Colombo, F., Avantifiori, R., Baldassarri, V., Caronna, R., Cicerchia, P. M., Corallino, D., Crocetti, D., Gallo, Giuseppe, Giovanardi, F., Giovannetti, F., Hassan, R., Iossa, A., Lai, Q., Lancellotti, F., Lucarini, A., Lucchese, S., Mazzarella, Giulio, Melandro, F., Minervini, A., Muttillo, E. M., Palmieri, L., Pasqua, R., Rosiello, F., Salina, Giulia, Sibio, S., Sirignano, P., Tarallo, M., Usai, S., Vanni, C., Viglietta, E., Zambon, M., Conversano, N. I., Epifani, A. G., Milano, Valentina, Sacco, L., Nava, Bruna Maria, Maffioli, A., Giuratrabocchetta, S., Baracchi, F., Zuolo, M., Ceresoli, M., Verdi, D., Belli, Andrea, Pata, F., Piovano, E., Pastore, G., Bernabei, F., Deiana, S., Arceri, A., D'Agostino, Cinzia, Marafante, C., Moggia, E., Parini, S., Moretti, M., Uggeri, F., Pontarolo, N., Fontana, T., Palmisano, Gerardo, Giuffrida, M., Guaitoli, E., Ferretti, C., Iacopino, G., Gioco, R., Roscitano, G., Montanelli, P., Chiappetta, M. F., Pinotti, E., Monati, E., Fazio, G., Di Pietro, F., Damarco, F., Barberis, A., Razzore, A., Pascale, A., Loi, S., Ferrara, F., Rossi, Marco, Lisi, G., Viel, G., Sasia, D., Bono, D., Cordaro, E. R., Giacomelli, E., Giani, I., Seriau, L., Pellino, Giuseppe, Sparavigna, M., Trigiante, G., D'Ambrogio, R. G., Cardella, F., Guzzetti, S., Luzzi, A. -P., Carganico, G., Drago, B., Micheletto, G., Orlandi, R., Cutolo, C., Gibello, U., Mistrangelo, M., Forcignano, E., D'Ugo, S., Losurdo, P., Manitto, M., Caroli, G., Franco, Manuela, Tilocca, P. L., Mendogni, P., Sena, G., Sambucci, D., Luciani, C., Atelli, P., Guida, Maria Antonietta, Marino, Filippo, Morini, A., Sibilla, M. G., Longo, Fabio, Giaccari, S., Vigorita, V., Balduzzi, A., Barra, F., Delogu, D., Milone, E., Bencini, L., Aprile, V., Papini, P., Montemurro, N., Cavallo, Michele, Picciariello, A., Tomasicchio, G., Fittipaldi, A., Maruccia, M., Gerardi, S., Cillara, N., Deidda, Silvia, Demarinis, G., Peiretti, E., Tatti, F., Iovino, C., Isola, G., Progno, V. C., Migliore, M., Badessi, G., Barilla, C., Calleri, G. S., Cianci, Stefano, Fama, F., Fleres, F., Mazzeo, C., Visaloco, M. G., Marchetto, C., Bolognesi, F., Benuzzi, L., Bracchetti, G., Brucchi, F., Manzo, C. A., Scaravilli, L., Ferrari, C., Rocca, A., Napolitano, Paola, Anoldo, P., Caricato, Chiara, Manigrasso, M., Milone, Maria, Napolitano, L., Palomba, G., Schiavone, V., Vetrella, M., Grossi, U., Moletta, L., Annicchiarico, A., Vella, I., Talesa, G., Boggi, U., Aiello, F., Anselmo, Anna, Bacchiocchi, G., Beati, F., Bellato, V., Billeci, F., Blasi, F., Buonomo, O. C., Campanelli, M., Coco, G., Contadini, A., Conte, L. E., D'Ippolito, G., Di Marcantonio, A., Spicchiale, C. F., Afflitto, G. G., Gismondi, A., Gorgolini, G., Granai, A. V., Grande, S., Gravina, A., Guida, A. M., Ingallinella, S., Keci, L., Latini, E., Marino, D., Oddi, F. M., Orecchia, L., Don, C. B. P., Pellicciaro, M., Petagna, L., Pirozzi, B. M., Quaranta, Caterina, Rho, M., Rosina, Alessandro, Santicchia, M. S., Saraceno, F., Schiavone, A., Sensi, B., Spina, A., Sullo, L., Tacconi, F., Taje, R., Vanni, G., Vinci, D., Vita, G., Alba, G., Badalucco, S., Carbone, Luigi, Samorani, O. C., Chisci, G., Cuomo, Rosa, Francia, A., Fusario, D., Gargiulo, B., Pasqui, E., Pasquetti, L., Puoti, P., Resca, L., Cumbo, J., Ganio, S., Vizzielli, Giuseppe, Anastasi, M., Guerra, D., Romanzi, A., Vannelli, A., Baia, M., Giordano L., Barone M., Corti S., Marangi G. (ORCID:0000-0002-6898-8882), Santini S. (ORCID:0000-0003-1956-5899), Ardito F. (ORCID:0000-0003-1596-2862), Belia F., Biondi A. (ORCID:0000-0002-2470-7858), Brisinda G. (ORCID:0000-0001-8820-9471), Ciolli A., Ferracci F., Fiorillo C. (ORCID:0000-0001-7681-3567), Fransvea P. (ORCID:0000-0003-4969-3373), La Greca A. (ORCID:0000-0002-7587-7427), Litta F., Panettieri E., Papa V. (ORCID:0000-0002-3709-8924), Patini R. (ORCID:0000-0001-7358-8763), Perrotta G., Puccioni C., Musumeci G., Berardi G., Ferretti S., Mariano G., Mangiameli G., Sacchi M. (ORCID:0000-0003-2826-8431), Di Carlo G., Paratore M., Ottaviani L. (ORCID:0009-0001-0967-8809), Gallo G., Mazzarella G., Salina G., Milano V., Nava M., Belli A., D'Agostino C., Palmisano G., Rossi M. (ORCID:0000-0002-4539-5670), Pellino G., Franco M., Guida A., Marino F., Longo F., Cavallo M., Deidda S., Cianci S., Napolitano P., Caricato C., Milone M., Anselmo A., Quaranta C., Rosina A. (ORCID:0000-0002-0158-0583), Carbone L., Cuomo R., Vizzielli G., Siragusa, L., Angelico, R., Angrisani, M., Zampogna, B., Materazzo, M., Sorge, R., Giordano, Lucia, Meniconi, R., Coppola, A., Marino, A., Giraudo, G., Esposito, S., Urbani, A., De Pastena, M., Mastrapasqua, R., Garancini, M., Frontal, A., Pascal, G., Martellucc, J., Falb, F., Boscarelli, A., Bertoglio, P., Trecca, E., Galassi, L., Vento, V., Chiappini, A., Antonelli, A., Bennardo, F., Familiari, F., Giannaccare, G., Zappia, A. S., Giuliani, G., Falcone, F., Sebastiani, S., Montuori, M., Rossi, S., Sagnotta, A., Giuliani, B., Imbriani, G. C., Restaino, S., Andreani, L., Di Maria, F., Lagana, A. S., Vitiello, L., Berton, F., Virgilio, E., Palisi, M., Portigliotti, L., Calussi, M., Conti, L., Mauriello, C., Barone, Alessia Maria Addolorata, Saladino, E., Giaquinta, A., Zerb, D., Frazzetta, G., Merola, G., Chierici, A., Bini, R., Centonze, L., De Carlis, R., Ferrario, L., Giani, A., Lauterio, A., Tamini, N., Corti, Serafino, Botteri, E., Andreuccetti, J., D'Alessio, R., Cestaro, G., Clarizia, G., Spolini, A., Carboni, A. S., Benzoni, E., Galiffa, G., Perotti, B., Veroux, M., Randazzo, V., Topa, D., Pranteda, C., Contini, G., Iacusso, C., Voglino, V., Vita, P., Carrano, F. M., Ambrosio, L., Cammarata, R., Capolupo, G. T., Caputo, D., Carannante, F., Cascone, C., Esperto, F., Farolfi, T., Frasca, L., Gallo, I. F., Gibin, G., Giurazza, G., Improta, L., La Vaccara, V., Luffarelli, P., Luvero, D., Marangi, Giuseppe, Masciana, G., Mazzola, A., Mazzotta, E., Miligi, C. I., Montelione, N., Nenna, A., Orsaria, P., Papalia, R., Papalia, G. F., Parisi, F. R., Prata, F., Salzillo, R., Santini, Stefano Angelo, Sofo, F., Zampoli, A., Tanda, C., Altieri, G., Ardito, Francesco, Belia, Francesco, Bianchi, V., Biondi, Alberto, Brisinda, Giuseppe, Chiappetta, M., Ciolli, G., Ciolli, Alessandro, Ferracci, Federica, Ferri, L., Fico, V., Fiorillo, Claudio, Fransvea, Pietro, Galiandro, F., Giovinazzo, F., La Greca, Antonio, Litta, Francesco, Mele, C., Pafundi, D. P., Panettieri, Elena, Papa, Valerio, Patini, Romeo, Perrotta, Generoso, Puccioni, Caterina, Santocchi, P., Armatura, G., Olmi, S., Casoni Pattacini, G., Salgarello, S., Trompetto, M., Bombardini, C., La Rocca, R., Celentano, G., Micalef, A., Mazzella, A., Settembrini, A., Zoia, C., Degrate, L., Musumeci, Giampaolo, Palopoli, C. A. M., Montori, G., Bonati, E., Dinuzzi, V. P., Velluti, F., Balla, A., Bonasia, D. E., Coletta, D., Berardi, Giulia, Colasanti, M., Ferretti, Serena, Gasparoli, C., Mariano, Giuseppantonio, Avenia, S., Cianci, P., Cestino, L., Festa, F., Fazio, F., Ascari, F., Desio, M., Arroyo Murillo, G. A., Cereda, M., Galleano, R., David, G., Pansini, A., Gazia, C., Atzori, G., Desideri, L. F., Famularo, S., Galvanin, J., Giudici, V. M., Mangiameli, Gaetano, Mei, S., Milana, F., Pansa, A., Sacchi, Dario Marco, Testori, A., Di Carlo, Giampiero, Paratore, Mattia, Perrone, U., Vagge, A., Vigano, J., Torre, B., Scotti, M. A., Carbone, G., Cerchione, R., De Nardi, P., Gozzini, L., Ottaviani, Letizia, Senni, C., Piccin, O., Pio, L., Colombo, F., Avantifiori, R., Baldassarri, V., Caronna, R., Cicerchia, P. M., Corallino, D., Crocetti, D., Gallo, Giuseppe, Giovanardi, F., Giovannetti, F., Hassan, R., Iossa, A., Lai, Q., Lancellotti, F., Lucarini, A., Lucchese, S., Mazzarella, Giulio, Melandro, F., Minervini, A., Muttillo, E. M., Palmieri, L., Pasqua, R., Rosiello, F., Salina, Giulia, Sibio, S., Sirignano, P., Tarallo, M., Usai, S., Vanni, C., Viglietta, E., Zambon, M., Conversano, N. I., Epifani, A. G., Milano, Valentina, Sacco, L., Nava, Bruna Maria, Maffioli, A., Giuratrabocchetta, S., Baracchi, F., Zuolo, M., Ceresoli, M., Verdi, D., Belli, Andrea, Pata, F., Piovano, E., Pastore, G., Bernabei, F., Deiana, S., Arceri, A., D'Agostino, Cinzia, Marafante, C., Moggia, E., Parini, S., Moretti, M., Uggeri, F., Pontarolo, N., Fontana, T., Palmisano, Gerardo, Giuffrida, M., Guaitoli, E., Ferretti, C., Iacopino, G., Gioco, R., Roscitano, G., Montanelli, P., Chiappetta, M. F., Pinotti, E., Monati, E., Fazio, G., Di Pietro, F., Damarco, F., Barberis, A., Razzore, A., Pascale, A., Loi, S., Ferrara, F., Rossi, Marco, Lisi, G., Viel, G., Sasia, D., Bono, D., Cordaro, E. R., Giacomelli, E., Giani, I., Seriau, L., Pellino, Giuseppe, Sparavigna, M., Trigiante, G., D'Ambrogio, R. G., Cardella, F., Guzzetti, S., Luzzi, A. -P., Carganico, G., Drago, B., Micheletto, G., Orlandi, R., Cutolo, C., Gibello, U., Mistrangelo, M., Forcignano, E., D'Ugo, S., Losurdo, P., Manitto, M., Caroli, G., Franco, Manuela, Tilocca, P. L., Mendogni, P., Sena, G., Sambucci, D., Luciani, C., Atelli, P., Guida, Maria Antonietta, Marino, Filippo, Morini, A., Sibilla, M. G., Longo, Fabio, Giaccari, S., Vigorita, V., Balduzzi, A., Barra, F., Delogu, D., Milone, E., Bencini, L., Aprile, V., Papini, P., Montemurro, N., Cavallo, Michele, Picciariello, A., Tomasicchio, G., Fittipaldi, A., Maruccia, M., Gerardi, S., Cillara, N., Deidda, Silvia, Demarinis, G., Peiretti, E., Tatti, F., Iovino, C., Isola, G., Progno, V. C., Migliore, M., Badessi, G., Barilla, C., Calleri, G. S., Cianci, Stefano, Fama, F., Fleres, F., Mazzeo, C., Visaloco, M. G., Marchetto, C., Bolognesi, F., Benuzzi, L., Bracchetti, G., Brucchi, F., Manzo, C. A., Scaravilli, L., Ferrari, C., Rocca, A., Napolitano, Paola, Anoldo, P., Caricato, Chiara, Manigrasso, M., Milone, Maria, Napolitano, L., Palomba, G., Schiavone, V., Vetrella, M., Grossi, U., Moletta, L., Annicchiarico, A., Vella, I., Talesa, G., Boggi, U., Aiello, F., Anselmo, Anna, Bacchiocchi, G., Beati, F., Bellato, V., Billeci, F., Blasi, F., Buonomo, O. C., Campanelli, M., Coco, G., Contadini, A., Conte, L. E., D'Ippolito, G., Di Marcantonio, A., Spicchiale, C. F., Afflitto, G. G., Gismondi, A., Gorgolini, G., Granai, A. V., Grande, S., Gravina, A., Guida, A. M., Ingallinella, S., Keci, L., Latini, E., Marino, D., Oddi, F. M., Orecchia, L., Don, C. B. P., Pellicciaro, M., Petagna, L., Pirozzi, B. M., Quaranta, Caterina, Rho, M., Rosina, Alessandro, Santicchia, M. S., Saraceno, F., Schiavone, A., Sensi, B., Spina, A., Sullo, L., Tacconi, F., Taje, R., Vanni, G., Vinci, D., Vita, G., Alba, G., Badalucco, S., Carbone, Luigi, Samorani, O. C., Chisci, G., Cuomo, Rosa, Francia, A., Fusario, D., Gargiulo, B., Pasqui, E., Pasquetti, L., Puoti, P., Resca, L., Cumbo, J., Ganio, S., Vizzielli, Giuseppe, Anastasi, M., Guerra, D., Romanzi, A., Vannelli, A., Baia, M., Giordano L., Barone M., Corti S., Marangi G. (ORCID:0000-0002-6898-8882), Santini S. (ORCID:0000-0003-1956-5899), Ardito F. (ORCID:0000-0003-1596-2862), Belia F., Biondi A. (ORCID:0000-0002-2470-7858), Brisinda G. (ORCID:0000-0001-8820-9471), Ciolli A., Ferracci F., Fiorillo C. (ORCID:0000-0001-7681-3567), Fransvea P. (ORCID:0000-0003-4969-3373), La Greca A. (ORCID:0000-0002-7587-7427), Litta F., Panettieri E., Papa V. (ORCID:0000-0002-3709-8924), Patini R. (ORCID:0000-0001-7358-8763), Perrotta G., Puccioni C., Musumeci G., Berardi G., Ferretti S., Mariano G., Mangiameli G., Sacchi M. (ORCID:0000-0003-2826-8431), Di Carlo G., Paratore M., Ottaviani L. (ORCID:0009-0001-0967-8809), Gallo G., Mazzarella G., Salina G., Milano V., Nava M., Belli A., D'Agostino C., Palmisano G., Rossi M. (ORCID:0000-0002-4539-5670), Pellino G., Franco M., Guida A., Marino F., Longo F., Cavallo M., Deidda S., Cianci S., Napolitano P., Caricato C., Milone M., Anselmo A., Quaranta C., Rosina A. (ORCID:0000-0002-0158-0583), Carbone L., Cuomo R., and Vizzielli G.

Abstract

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March–April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients’ management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons’ personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon–patient/family communication. From the Italian surgeons’ perspective, COVID-related measures will continue to influence

Published
2023

15. Linear Diagnostic Procedure Elicited by Clinical Genetics and Validated by mRNA Analysis in Neuronal Ceroid Lipofuscinosis 7 Associated with a Novel Non-Canonical Splice Site Variant in MFSD8

Author

Pasquetti, Domizia, primary, Marangi, Giuseppe, additional, Orteschi, Daniela, additional, Carapelle, Marina, additional, L’Erario, Federica Francesca, additional, Venditti, Romina, additional, Maietta, Sabrina, additional, Battaglia, Domenica Immacolata, additional, Contaldo, Ilaria, additional, Veredice, Chiara, additional, and Zollino, Marcella, additional

Published
2023
Full Text
View/download PDF

17. Novel variants and cellular studies on patients' primary fibroblasts support a role for NEK1 missense variants in ALS pathogenesis

Author

Lattante, Serena, Doronzio, Paolo Niccolo', Conte, Amelia, Marangi, Giuseppe, Martello, Francesco, Bisogni, Giulia, Meleo, Emiliana, Colavito, Davide, Del Giudice, Elda, Patanella, Agata Katia, Bernardo, Daniela, Romano, Angela, Zollino, Marcella, Sabatelli, Mario, Lattante, Serena (ORCID:0000-0003-2891-0340), Doronzio, Paolo Niccolò, Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Zollino, Marcella (ORCID:0000-0003-4871-9519), Sabatelli, Mario (ORCID:0000-0001-6635-4985), Lattante, Serena, Doronzio, Paolo Niccolo', Conte, Amelia, Marangi, Giuseppe, Martello, Francesco, Bisogni, Giulia, Meleo, Emiliana, Colavito, Davide, Del Giudice, Elda, Patanella, Agata Katia, Bernardo, Daniela, Romano, Angela, Zollino, Marcella, Sabatelli, Mario, Lattante, Serena (ORCID:0000-0003-2891-0340), Doronzio, Paolo Niccolò, Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Zollino, Marcella (ORCID:0000-0003-4871-9519), and Sabatelli, Mario (ORCID:0000-0001-6635-4985)

Abstract

In the last few years, NEK1 has been identified as a new gene related to amyotrophic lateral sclerosis (ALS). Loss-of-function variants have been mostly described, although several missense variants exist, which pathogenic relevance remains to be established. We attempted to determine the contribution of NEK1 gene in an Italian cohort of 531 sporadic and familial amyotrophic lateral sclerosis (ALS) patients applying massive parallel sequencing technologies. We filtered results of NEK1 gene and identified 20 NEK1 rare variants (MAF <0.01) in 22 patients. In particular, we found two novel frameshift variants (p.Glu929Asnfs*12 and p.Val1030Ilefs*23), 18 missense variants, including the p.Arg261His in three patients, and a novel variant in the start codon, the p.Met1?, which most likely impairs translation initiation. To clarify the role of NEK1 missense variants we investigated NEK1 expression in primary fibroblast cultures. We obtained skin biopsies from four patients with NEK1 variants and we assessed NEK1 expression by Western Blot and immunofluorescence. We detected a decrease in NEK1 expression in fibroblasts from patients with NEK1 variants, suggesting that missense variants in NEK1 gene may have a pathogenic role. Moreover, we observed additional variants in ALS related genes in seven patients with NEK1 variants (32%), further supporting an oligogenic ALS model.

Published
2021

18. A novel truncating variant within exon 7 of KAT6B associated with features of both Say–Barber–Bieseker–Young–Simpson syndrome and genitopatellar syndrome: Further evidence of a continuum in the clinical spectrum of KAT6B‐related disorders

Author

Marangi, Giuseppe, Di Giacomo, Marilena C., Lattante, Serena, Orteschi, Daniela, Patrizi, Sara, Doronzio, Paolo N., Riviello, Francesco N., Vaisfeld, Alessandro, Frangella, Silvia, and Zollino, Marcella

Published
2018
Full Text
View/download PDF

19. Analysis of STMN2 CA repeats in italian ALS patients shows no association

Author

Doronzio, Paolo Niccolò, primary, Lattante, Serena, additional, Marangi, Giuseppe, additional, Martello, Francesco, additional, Conte, Amelia, additional, Bisogni, Giulia, additional, Bernardo, Daniela, additional, Patanella, Agata Katia, additional, Meleo, Emiliana, additional, Zollino, Marcella, additional, and Sabatelli, Mario, additional

Published
2022
Full Text
View/download PDF

20. Generation of an induced pluripotent stem cell line (UCSCi002-A) from a patient with a variant in TARDBP gene associated with familial amyotrophic lateral sclerosis and frontotemporal dementia

Author

Martello, Francesco, primary, Lattante, Serena, additional, Doronzio, Paolo Niccolò, additional, Conte, Amelia, additional, Bisogni, Giulia, additional, Orteschi, Daniela, additional, Luigetti, Marco, additional, Marrucci, Maria Alessandra, additional, Zollino, Marcella, additional, Sabatelli, Mario, additional, and Marangi, Giuseppe, additional

Published
2022
Full Text
View/download PDF

21. SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Author

Cordovado, Amélie, primary, Schaettin, Martina, additional, Jeanne, Médéric, additional, Panasenkava, Veranika, additional, Denommé-Pichon, Anne-Sophie, additional, Keren, Boris, additional, Mignot, Cyril, additional, Doco-Fenzy, Martine, additional, Rodan, Lance, additional, Ramsey, Keri, additional, Narayanan, Vinodh, additional, Jones, Julie R, additional, Prijoles, Eloise J, additional, Mitchell, Wendy G, additional, Ozmore, Jillian R, additional, Juliette, Kali, additional, Torti, Erin, additional, Normand, Elizabeth A, additional, Granger, Leslie, additional, Petersen, Andrea K, additional, Au, Margaret G, additional, Matheny, Juliann P, additional, Phornphutkul, Chanika, additional, Chambers, Mary-Kathryn, additional, Fernández-Ramos, Joaquín-Alejandro, additional, López-Laso, Eduardo, additional, Kruer, Michael C, additional, Bakhtiari, Somayeh, additional, Zollino, Marcella, additional, Morleo, Manuela, additional, Marangi, Giuseppe, additional, Mei, Davide, additional, Pisano, Tiziana, additional, Guerrini, Renzo, additional, Louie, Raymond J, additional, Childers, Anna, additional, Everman, David B, additional, Isidor, Betrand, additional, Audebert-Bellanger, Séverine, additional, Odent, Sylvie, additional, Bonneau, Dominique, additional, Gilbert-Dussardier, Brigitte, additional, Redon, Richard, additional, Bézieau, Stéphane, additional, Laumonnier, Frédéric, additional, Stoeckli, Esther T, additional, Toutain, Annick, additional, and Vuillaume, Marie-Laure, additional

Published
2022
Full Text
View/download PDF

22. Deregulated expression of the imprinted DLK1-DIO3 region in Glioblastoma Stem-like Cells: tumor suppressor role of lncRNA MEG3

Author

Buccarelli, Mariachiara, Lulli, Valentina, Giuliani, Alessandro, Signore, Michele, Martini, Maurizio, D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Novelli, Agnese, Ilari, Ramona, Giurato, Giorgio, Boe, Alessandra, Castellani, Giorgia, Spartano, Serena, Marangi, Giuseppe, Biffoni, Mauro, Genuardi, Maurizio, Pallini, Roberto, Marziali, Giovanna, Ricci-Vitiani, Lucia, Martini, Maurizio (ORCID:0000-0002-6260-6310), D'Alessandris, Quintino G (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Genuardi, Maurizio (ORCID:0000-0002-7410-8351), Pallini, Roberto (ORCID:0000-0002-4611-8827), Buccarelli, Mariachiara, Lulli, Valentina, Giuliani, Alessandro, Signore, Michele, Martini, Maurizio, D'Alessandris, Quintino Giorgio, Giannetti, Stefano, Novelli, Agnese, Ilari, Ramona, Giurato, Giorgio, Boe, Alessandra, Castellani, Giorgia, Spartano, Serena, Marangi, Giuseppe, Biffoni, Mauro, Genuardi, Maurizio, Pallini, Roberto, Marziali, Giovanna, Ricci-Vitiani, Lucia, Martini, Maurizio (ORCID:0000-0002-6260-6310), D'Alessandris, Quintino G (ORCID:0000-0002-2953-9291), Giannetti, Stefano (ORCID:0000-0002-9456-8865), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Genuardi, Maurizio (ORCID:0000-0002-7410-8351), and Pallini, Roberto (ORCID:0000-0002-4611-8827)

Abstract

Background: Glioblastoma (GBM) stem-like cells (GSCs) are thought to be responsible for the maintenance and aggressiveness of GBM, the most common primary brain tumor in adults. This study aims at elucidating the involvement of deregulations within the imprinted DLK-DIO3 region on chromosome 14q32 in GBM pathogenesis. Methods: RT-PCR analyses were performed on GSCs and GBM tissues. Methylation analyses, gene expression and Reverse-Phase protein Array profiles were used to investigate the tumor suppressor function of MEG3. Results: Loss of expression of genes and non-coding RNAs within the DLK1-DIO3 region was observed in GSCs and GBM tissues compared to normal brain. This down-regulation is mainly mediated by epigenetic silencing. Kaplan-Meier analysis indicated that low expression of MEG3 and MEG8 lncRNAs significantly correlated with short survival in GBM patients. MEG3 restoration impairs tumorigenic abilities of GSCs in vitro by inhibiting cell growth, migration and colony formation and decreases in vivo tumor growth reducing infiltrative growth. These effects were associated with modulation of genes involved in cell adhesion and Epithelial to Mesenchymal Transition (EMT). Conclusions: In GBM, MEG3 acts as a tumor-suppressor mainly regulating cell adhesion, EMT and cell proliferation, thus providing a potential candidate for novel GBM therapies.

Published
2020

23. SOD1 p.D12Y variant is associated with ALS/distal myopathy spectrum

Author

Tasca, Giorgio, Lattante, Serena, Marangi, Giuseppe, Conte, Amelia, Bernardo, Daniela, Bisogni, Giulia, Mandich, Paola, Zollino, Marcella, Ragozzino, Elvira, Udd, Bjarne, Sabatelli, Mario, Lattante, Serena (ORCID:0000-0003-2891-0340), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Zollino, Marcella (ORCID:0000-0003-4871-9519), Sabatelli, Mario (ORCID:0000-0001-6635-4985), Tasca, Giorgio, Lattante, Serena, Marangi, Giuseppe, Conte, Amelia, Bernardo, Daniela, Bisogni, Giulia, Mandich, Paola, Zollino, Marcella, Ragozzino, Elvira, Udd, Bjarne, Sabatelli, Mario, Lattante, Serena (ORCID:0000-0003-2891-0340), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Zollino, Marcella (ORCID:0000-0003-4871-9519), and Sabatelli, Mario (ORCID:0000-0001-6635-4985)

Abstract

BACKGROUND: The aim of our study was to describe patients with the p.D12Y variant (previously reported as D11Y) in SOD1 disclosing heterogeneous clinicopathological features. METHODS: We performed clinical, electrophysiological, MRI and muscle pathology studies in four SOD1 p.D12Y variant positive patients. RESULTS: SOD1 p.D12Y clinical manifestations ranged from a benign phenotype characterized by distal distribution of muscular weakness and long survival to classic forms of amyotrophic lateral sclerosis with poor prognosis. Two patients with the distal clinical phenotype showed MRI and muscle pathology alterations indicating a concurrent muscle involvement. In one of these patients significant myopathic changes were associated with rimmed vacuolar pathology. CONCLUSIONS: We expand the clinical spectrum of SOD1 p.D12Y variant, including predominant lower motor neuron forms with long survival and classic forms with aggressive course. Some patients may have concomitant distal myopathy without other explanations. Given clinical, MRI and muscle pathology alterations SOD1 should be considered in the differential diagnosis of molecularly undefined distal myopathies with rimmed vacuoles.

Published
2020

25. Generation of an induced pluripotent stem cell line (UCSCi002-A) from a patient with a variant in TARDBP gene associated with familial amyotrophic lateral sclerosis and frontotemporal dementia

Author

Martello, Francesco, Lattante, Serena, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Orteschi, D., Luigetti, Marco, Marrucci, M. A., Zollino, Marcella, Sabatelli, Mario, Marangi, Giuseppe, Martello F., Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Luigetti M. (ORCID:0000-0001-7539-505X), Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), Marangi G. (ORCID:0000-0002-6898-8882), Martello, Francesco, Lattante, Serena, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Orteschi, D., Luigetti, Marco, Marrucci, M. A., Zollino, Marcella, Sabatelli, Mario, Marangi, Giuseppe, Martello F., Lattante S. (ORCID:0000-0003-2891-0340), Doronzio P. N., Luigetti M. (ORCID:0000-0001-7539-505X), Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), and Marangi G. (ORCID:0000-0002-6898-8882)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that selectively affects motor neurons. In 20% of cases, ALS appears in comorbidity with frontotemporal dementia (FTD). We generated patient-derived-induced Pluripotent Stem Cells (iPSCs), from an ALS/FTD patient. The patient had a familial form of the disease and a missense variant in TARDBP gene. We used an established protocol based on Sendai virus to reprogram fibroblasts. We confirmed the stemness and the pluripotency of the iPSC clones, thus generating embryoid bodies. We believe that the iPSC line carrying a TARDBP mutation could be a valuable tool to investigate TDP-43 proteinopathy linked to ALS.

Published
2022

26. SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Author

Cordovado, A., Schaettin, M., Jeanne, M., Panasenkava, V., Denomme-Pichon, A. -S., Keren, B., Mignot, C., Doco-Fenzy, M., Rodan, L., Ramsey, K., Narayanan, V., Jones, J. R., Prijoles, E. J., Mitchell, W. G., Ozmore, J. R., Juliette, K., Torti, E., Normand, E. A., Granger, L., Petersen, A. K., Au, M. G., Matheny, J. P., Phornphutkul, C., Chambers, M. -K., Fernandez-Ramos, J. -A., Lopez-Laso, E., Kruer, M. C., Bakhtiari, S., Zollino, Marcella, Morleo, M., Marangi, Giuseppe, Mei, D., Pisano, T., Guerrini, R., Louie, R. J., Childers, A., Everman, D. B., Isidor, B., Audebert-Bellanger, S., Odent, S., Bonneau, D., Gilbert-Dussardier, B., Redon, R., Bezieau, S., Laumonnier, F., Stoeckli, E. T., Toutain, A., Vuillaume, M. -L., Zollino M. (ORCID:0000-0003-4871-9519), Marangi G. (ORCID:0000-0002-6898-8882), Cordovado, A., Schaettin, M., Jeanne, M., Panasenkava, V., Denomme-Pichon, A. -S., Keren, B., Mignot, C., Doco-Fenzy, M., Rodan, L., Ramsey, K., Narayanan, V., Jones, J. R., Prijoles, E. J., Mitchell, W. G., Ozmore, J. R., Juliette, K., Torti, E., Normand, E. A., Granger, L., Petersen, A. K., Au, M. G., Matheny, J. P., Phornphutkul, C., Chambers, M. -K., Fernandez-Ramos, J. -A., Lopez-Laso, E., Kruer, M. C., Bakhtiari, S., Zollino, Marcella, Morleo, M., Marangi, Giuseppe, Mei, D., Pisano, T., Guerrini, R., Louie, R. J., Childers, A., Everman, D. B., Isidor, B., Audebert-Bellanger, S., Odent, S., Bonneau, D., Gilbert-Dussardier, B., Redon, R., Bezieau, S., Laumonnier, F., Stoeckli, E. T., Toutain, A., Vuillaume, M. -L., Zollino M. (ORCID:0000-0003-4871-9519), and Marangi G. (ORCID:0000-0002-6898-8882)

Abstract

Intellectual disability (ID) is a neurodevelopmental disorder frequently caused by monogenic defects. In this study, we collected 14 SEMA6B heterozygous variants in 16 unrelated patients referred for ID to different centers. Whereas, until now, SEMA6B variants have mainly been reported in patients with progressive myoclonic epilepsy, our study indicates that the clinical spectrum is wider and also includes non-syndromic ID without epilepsy or myoclonus. To assess the pathogenicity of these variants, selected mutated forms of Sema6b were overexpressed in Human Embryonic Kidney 293T (HEK293T) cells and in primary neuronal cultures. shRNAs targeting Sema6b were also used in neuronal cultures to measure the impact of the decreased Sema6b expression on morphogenesis and synaptogenesis. The overexpression of some variants leads to a subcellular mislocalization of SEMA6B protein in HEK293T cells and to a reduced spine density owing to loss of mature spines in neuronal cultures. Sema6b knockdown also impairs spine density and spine maturation. In addition, we conducted in vivo rescue experiments in chicken embryos with the selected mutated forms of Sema6b expressed in commissural neurons after knockdown of endogenous SEMA6B. We observed that expression of these variants in commissural neurons fails to rescue the normal axon pathway. In conclusion, identification of SEMA6B variants in patients presenting with an overlapping phenotype with ID and functional studies highlight the important role of SEMA6B in neuronal development, notably in spine formation and maturation and in axon guidance. This study adds SEMA6B to the list of ID-related genes.

Published
2022

27. International meeting on Wolf‐Hirschhorn syndrome: Update on the nosology and new insights on the pathogenic mechanisms for seizures and growth delay

Author

Nevado, J., K. S., Ho, Zollino, Marcella, Blanco, R., Cobaleda, C., Golzio, C., Beaudry-Bellefeuille, I., Berrocoso, S., Limeres, J., Barruz, P., Serrano-Martin, C., Cafiero, C., Malaga, I., Marangi, Giuseppe, Campos-Sanchez, E., Moriyon-Iglesias, T., Marquez, S., Markham, L., Twede, H., Lortz, A., Olson, L., Sheng, X., Weng, C., Wassman, E. R., Newcomb, T., Carey, J. C., Battaglia, A., Lopez-Granados, E., Douglas, D., and Lapunzina, P.

Subjects
0301 basic medicine, Nosology, medicine.medical_specialty, hepatoadenomas, 030105 genetics & heredity, 4p, Settore MED/03 - GENETICA MEDICA, medicine.disease, University hospital, 03 medical and health sciences, 030104 developmental biology, antiepileptic drugs, seizures, WHS, Family medicine, Genetics, medicine, Psychology, Wolf–Hirschhorn syndrome, Genetics (clinical), Panel discussion, Theme (narrative)
Abstract

"An International Meeting on Wolf-Hirschhorn Syndrome (WHS)" was held at The University Hospital La Paz in Madrid, Spain (October 13-14, 2017). One hundred and twenty-five people, including physicians, scientists and affected families, attended the meeting. Parent and patient advocates from the Spanish Association of WHS opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes. These proceedings will review the major points of discussion.

Published
2019

31. Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype–phenotype correlations in a large cohort of patients

Author

Zollino, Marcella, Marangi, Giuseppe, Ponzi, Emanuela, Orteschi, Daniela, Ricciardi, Stefania, Lattante, Serena, Murdolo, Marina, Battaglia, Domenica, Contaldo, Ilaria, Mercuri, Eugenio, Stefanini, Maria Chiara, Caumes, Roseline, Edery, Patrick, Rossi, Massimiliano, Piccione, Maria, Corsello, Giovanni, Della Monica, Matteo, Scarano, Francesca, Priolo, Manuela, Gentile, Mattia, Zampino, Giuseppe, Vijzelaar, Raymon, Abdulrahman, Omar, Rauch, Anita, Oneda, Beatrice, Deardorff, Matthew A, Saitta, Sulagna C, Falk, Marni J, Dubbs, Holly, and Zackai, Elaine

Published
2015
Full Text
View/download PDF

32. Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement

Author

Zollino, Marcella, Zweier, Christiane, Van Balkom, Ingrid D., Sweetser, David A., Alaimo, Joseph, Bijlsma, Emilia K., Cody, Jannine, Elsea, Sarah H., Giurgea, Irina, Macchiaiolo, Marina, Smigiel, Robert, Thibert, Ronald L., Benoist, Ingrid, Clayton-Smith, Jill, De Winter, Channa F., Deckers, Stijn, Gandhi, Anusha, Huisman, Sylvia, Kempink, Dagmar, Kruisinga, Frea, Lamacchia, Vittoria, Marangi, Giuseppe, Menke, Leonie, Mulder, Paul, Nordgren, Ann, Renieri, Alessandra, Routledge, Sue, Saunders, Carol J., Stembalska, Agnieszka, Van Balkom, Han, Whalen, Sandra, Hennekam, Raoul C., Zollino, Marcella (ORCID:0000-0003-4871-9519), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Zollino, Marcella, Zweier, Christiane, Van Balkom, Ingrid D., Sweetser, David A., Alaimo, Joseph, Bijlsma, Emilia K., Cody, Jannine, Elsea, Sarah H., Giurgea, Irina, Macchiaiolo, Marina, Smigiel, Robert, Thibert, Ronald L., Benoist, Ingrid, Clayton-Smith, Jill, De Winter, Channa F., Deckers, Stijn, Gandhi, Anusha, Huisman, Sylvia, Kempink, Dagmar, Kruisinga, Frea, Lamacchia, Vittoria, Marangi, Giuseppe, Menke, Leonie, Mulder, Paul, Nordgren, Ann, Renieri, Alessandra, Routledge, Sue, Saunders, Carol J., Stembalska, Agnieszka, Van Balkom, Han, Whalen, Sandra, Hennekam, Raoul C., Zollino, Marcella (ORCID:0000-0003-4871-9519), and Marangi, Giuseppe (ORCID:0000-0002-6898-8882)

Abstract

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care.

Published
2019

33. Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss

Author

Richard, Elodie M., primary, Bakhtiari, Somayeh, additional, Marsh, Ashley P.L., additional, Kaiyrzhanov, Rauan, additional, Wagner, Matias, additional, Shetty, Sheetal, additional, Pagnozzi, Alex, additional, Nordlie, Sandra M., additional, Guida, Brandon S., additional, Cornejo, Patricia, additional, Magee, Helen, additional, Liu, James, additional, Norton, Bethany Y., additional, Webster, Richard I., additional, Worgan, Lisa, additional, Hakonarson, Hakon, additional, Li, Jiankang, additional, Guo, Yiran, additional, Jain, Mahim, additional, Blesson, Alyssa, additional, Rodan, Lance H., additional, Abbott, Mary-Alice, additional, Comi, Anne, additional, Cohen, Julie S., additional, Alhaddad, Bader, additional, Meitinger, Thomas, additional, Lenz, Dominic, additional, Ziegler, Andreas, additional, Kotzaeridou, Urania, additional, Brunet, Theresa, additional, Chassevent, Anna, additional, Smith-Hicks, Constance, additional, Ekstein, Joseph, additional, Weiden, Tzvi, additional, Hahn, Andreas, additional, Zharkinbekova, Nazira, additional, Turnpenny, Peter, additional, Tucci, Arianna, additional, Yelton, Melissa, additional, Horvath, Rita, additional, Gungor, Serdal, additional, Hiz, Semra, additional, Oktay, Yavuz, additional, Lochmuller, Hanns, additional, Zollino, Marcella, additional, Morleo, Manuela, additional, Marangi, Giuseppe, additional, Nigro, Vincenzo, additional, Torella, Annalaura, additional, Pinelli, Michele, additional, Amenta, Simona, additional, Husain, Ralf A., additional, Grossmann, Benita, additional, Rapp, Marion, additional, Steen, Claudia, additional, Marquardt, Iris, additional, Grimmel, Mona, additional, Grasshoff, Ute, additional, Korenke, G. Christoph, additional, Owczarek-Lipska, Marta, additional, Neidhardt, John, additional, Radio, Francesca Clementina, additional, Mancini, Cecilia, additional, Claps Sepulveda, Dianela Judith, additional, McWalter, Kirsty, additional, Begtrup, Amber, additional, Crunk, Amy, additional, Guillen Sacoto, Maria J., additional, Person, Richard, additional, Schnur, Rhonda E., additional, Mancardi, Maria Margherita, additional, Kreuder, Florian, additional, Striano, Pasquale, additional, Zara, Federico, additional, Chung, Wendy K., additional, Marks, Warren A., additional, van Eyk, Clare L., additional, Webber, Dani L., additional, Corbett, Mark A., additional, Harper, Kelly, additional, Berry, Jesia G., additional, MacLennan, Alastair H., additional, Gecz, Jozef, additional, Tartaglia, Marco, additional, Salpietro, Vincenzo, additional, Christodoulou, John, additional, Kaslin, Jan, additional, Padilla-Lopez, Sergio, additional, Bilguvar, Kaya, additional, Munchau, Alexander, additional, Ahmed, Zubair M., additional, Hufnagel, Robert B., additional, Fahey, Michael C., additional, Maroofian, Reza, additional, Houlden, Henry, additional, Sticht, Heinrich, additional, Mane, Shrikant M., additional, Rad, Aboulfazl, additional, Vona, Barbara, additional, Jin, Sheng Chih, additional, Haack, Tobias B., additional, Makowski, Christine, additional, Hirsch, Yoel, additional, Riazuddin, Saima, additional, and Kruer, Michael C., additional

Published
2021
Full Text
View/download PDF

34. Generation of an induced pluripotent stem cell line (UCSCi001-A) from a patient with early-onset amyotrophic lateral sclerosis carrying a FUS variant

Author

Martello, Francesco, primary, Lattante, Serena, additional, Doronzio, Paolo Niccolò, additional, Conte, Amelia, additional, Bisogni, Giulia, additional, Orteschi, Daniela, additional, Pirozzi, Filomena, additional, Sabatelli, Mario, additional, Zollino, Marcella, additional, and Marangi, Giuseppe, additional

Published
2021
Full Text
View/download PDF

35. TBK1 is associated with ALS and ALS-FTD in Sardinian patients

Author

Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Capasso, Margherita, Caponnetto, Claudia, Mandich, Paolo, Mancardi, Gianluigi, Origone, Paola, Conforti, Francesca L., Vita, Giuseppe, Messina, Sonia, Russo, Massimo, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Lunetta, Christian, Penco, Silvana, Mosca, Lorena, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Tremolizzo, Lucio, Ferrarese, Carlo, Fini, Nicola, Fasano, Antonio, Monsurrò, Maria Rosaria, Tedeschi, Gioacchino, Trojsi, Francesca, Piccirillo, Giovanni, Cristillo, Viviana, Mazzini, Letizia, D'Alfonso, Sandra, Bersano, Anna, Corrado, Lucia, Bagarotti, Alessandra, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Ilardi, Antonio, Bertuzzo, Davide, Tanel, Raffaella, Pisano, Fabrizio, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Pirisi, Angelo, Parish, Leslie D., Ortu, Enzo, Borghero, Giuseppe, Pugliatti, Maura, Marrosu, Francesco, Marrosu, Maria Giovanna, Murru, Maria Rita, Floris, Gianluca, Cannas, Antonino, Occhineri, Patrizia, Cau, Tea B., Loi, Daniela, Ticca, Anna, Traccis, Sebastiano, Manera, Umberto, Canosa, Antonio, Moglia, Cristina, Calvo, Andrea, Barberis, Marco, Brunetti, Maura, Gibbs, J. Raphael, Renton, Alan E., Errichiello, Edoardo, Zoledziewska, Magdalena, Mulas, Antonella, Qian, Yong, Din, Jun, Pliner, Hannah A., Traynor, Bryan J., and Chiò, Adriano

Published
2016
Full Text
View/download PDF

36. Risultati di attivazione del processo. La valutazione

Author

Pier Cesare Rivoltella, Gianluca Braga, Alessandra Carenzio, Emilio Ghittoni, Sara Lo Jacono, Michele Marangi, Giuseppe Masengo, Eleonora Mazzotti, Isnaba Joana Miranda, Rosaria Pace, Gianna Pasquero, Stefano Pasta, Marco Rondonotti, Andrea Veronelli, Braga, Gianluca, Gianluca Braga (ORCID:0000-0001-7267-1274), Pier Cesare Rivoltella, Gianluca Braga, Alessandra Carenzio, Emilio Ghittoni, Sara Lo Jacono, Michele Marangi, Giuseppe Masengo, Eleonora Mazzotti, Isnaba Joana Miranda, Rosaria Pace, Gianna Pasquero, Stefano Pasta, Marco Rondonotti, Andrea Veronelli, Braga, Gianluca, and Gianluca Braga (ORCID:0000-0001-7267-1274)

Abstract

Participatory evaluation as a mean to facilitate the development of a community and a sense of belonging

Published
2021

37. Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Author

Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, Zucchi, Elisabetta, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson, Janel O, Chia, Ruth, Miller, Danny E, Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Troakes, Claire, Jones, Ashley R, Shatunov, Aleksey, Iacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P, Dobson-Stone, Carol, Kwok, John B, Bonkowski, Emily S, Palvadeau, Robin, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Al-Chalabi, Ammar, Brown, Robert H, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J, Perlman, Seth J, Glass, Ian, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, McLaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesús, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexis, Broach, James, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, DeMarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta

Abstract

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective: To identify the genetic variants associated with juvenile ALS. Design, setting, and participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main outcomes and measures: De novo variants present only in the index case and not in unaffected family members. Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis

Published
2021

38. Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization

Author

Tabolacci, Elisabetta, Molinario, C, Marangi, Giuseppe, Nobile, Veronica, Arena, Vincenzo, Mendes, Mi, Smith, Dec, Salomons, G, Tana, Milena, Costa, S, Vento, Giovanni, Genuardi, Maurizio, Tabolacci E (ORCID:0000-0002-4707-2242), Marangi G (ORCID:0000-0002-6898-8882), Nobile V, Arena V (ORCID:0000-0002-7562-223X), Tana M, Vento G (ORCID:0000-0002-8132-5127), Genuardi M. (ORCID:0000-0002-7410-8351), Tabolacci, Elisabetta, Molinario, C, Marangi, Giuseppe, Nobile, Veronica, Arena, Vincenzo, Mendes, Mi, Smith, Dec, Salomons, G, Tana, Milena, Costa, S, Vento, Giovanni, Genuardi, Maurizio, Tabolacci E (ORCID:0000-0002-4707-2242), Marangi G (ORCID:0000-0002-6898-8882), Nobile V, Arena V (ORCID:0000-0002-7562-223X), Tana M, Vento G (ORCID:0000-0002-8132-5127), and Genuardi M. (ORCID:0000-0002-7410-8351)

Abstract

No abstract available

Published
2021

39. CDKL5 mutations may mimic Pitt-Hopkins syndrome phenotype

Author

Curro, A., Doddato, G., Bruttini, M., Zollino, Marcella, Marangi, Giuseppe, Zappella, M., Renieri, A., Pinto, A. M., Zollino M. (ORCID:0000-0003-4871-9519), Marangi G. (ORCID:0000-0002-6898-8882), Curro, A., Doddato, G., Bruttini, M., Zollino, Marcella, Marangi, Giuseppe, Zappella, M., Renieri, A., Pinto, A. M., Zollino M. (ORCID:0000-0003-4871-9519), and Marangi G. (ORCID:0000-0002-6898-8882)

Abstract

Genetic conditions comprise a wide spectrum of different phenotypes, rapidly expanding due to new diagnostic methodologies. Patients’ facial features and clinical history represent the key elements leading clinicians to the right diagnosis. CDKL5-early onset epilepsy and Pitt-Hopkins syndrome are two well-known genetic conditions, with a defined phenotype sharing some common characteristics like early-onset epilepsy and hyperventilation episodes. Whilst facial features represent a diagnostic handle in patients with Pitt-Hopkins syndrome, clinical history is crucial in patients carrying a mutation in CDKL5. Here we present the clinical case of a girl evaluated for the first time when she was 24-years old, with a clinical phenotype mimicking Pitt-Hopkins syndrome. Her facial features have become coarser while she was growing up, leading geneticists to raise different clinical hypotheses and to perform several molecular tests before getting the diagnosis of CDKL5-early-epileptic encephalopathy. This finding highlights that although typical facial gestalt has not so far extensively been described in CDKL5 mutated adult patients, peculiar facial features could be present later in life and may let CDKL5-related disorder mimic Pitt Hopkins. Thus, considering atypical Rett syndrome in the differential diagnosis of Pitt Hopkins syndrome could be important to solve complex clinical cases.

Published
2021

40. CHARGE-like presentation, craniosynostosis and mild Mowat–Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases

Author

Wenger, Tara L., Harr, Margaret, Ricciardi, Stefania, Bhoj, Elizabeth, Santani, Avni, Adam, Margaret P., Barnett, Sarah S., Ganetzky, Rebecca, McDonald-McGinn, Donna M., Battaglia, Domenica, Bigoni, Stefania, Selicorni, Angelo, Sorge, Giovanni, Monica, Matteo Della, Mari, Francesca, Andreucci, Elena, Romano, Silvia, Cocchi, Guido, Savasta, Salvatore, Malbora, Baris, Marangi, Giuseppe, Garavelli, Livia, Zollino, Marcella, and Zackai, Elaine H.

Published
2014
Full Text
View/download PDF

43. Genetic counselling in ALS: facts, uncertainties and clinical suggestions

Author

Chiò, Adriano, Battistini, Stefania, Calvo, Andrea, Caponnetto, Claudia, Conforti, Francesca L, Corbo, Massimo, Giannini, Fabio, Mandrioli, Jessica, Mora, Gabriele, Sabatelli, Mario, Monsurrò, Maria Rosaria, Tedeschi, Gioacchino, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Volanti, Paolo, Marinou, Kalliopi, Papetti, Laura, Lunetta, Christian, Pintor, Giuseppe Lauria, Salvi, Fabrizio, Bartolomei, Ilaria, Quattrone, Aldo, Gambardella, Antonio, Logroscino, Giancarlo, Simone, Isabella, Pisano, Fabrizio, Spataro, Rossella, La Bella, Vincenzo, Colletti, Tiziana, Mancardi, Gianluigi, Origone, Paola, Sola, Patrizia, Borghero, Giuseppe, Marrosu, Francesco, Marrosu, Maria Giovanna, Murru, Maria Rita, Floris, Gianluca, Cannas, Antonino, Piras, Valeria, Costantino, Emanuela, Pani, Carla, Sotgiu, Maria Alessandra, Pugliatti, Maura, Parish, Leslie D., Cossu, Paola, Ticca, Anna, Rodolico, Carmelo, Portaro, Simona, Ricci, Claudia, Moglia, Cristina, Ossola, Irene, Brunetti, Maura, Barberis, Marco, Canosa, Antonio, Cammarosano, Stefania, Bertuzzo, Davide, Fuda, Giuseppe, Ilardi, Antonio, Manera, Umberto, Pastore, Ilaria, Sproviero, William, Logullo, Francesco, Tanel, Raffaella, Ajmone, Clara, Mastro, Enza, Pain, Debora, Mandich, Paola, Penco, Silvana, Restagno, Gabriella, Zollino, Marcella, and Surbone, Antonella

Published
2014
Full Text
View/download PDF

46. SYT1-associated neurodevelopmental disorder: A case series

Author

Baker, Kate, Gordon, Sarah L., Melland, Holly, Bumbak, Fabian, Scott, Daniel J., Jiang, Tess J., Owen, David, Turner, Bradley J., Boyd, Stewart G., Rossi, Mari, Al-Raqad, Mohammed, Elpeleg, Orly, Peck, Dawn, Mancini, Grazia M. S., Wilke, Martina, Zollino, Marcella, Marangi, Giuseppe, Weigand, Heike, Borggraefe, Ingo, Haack, Tobia, Stark, Zornitza, Sadedin, Simon, Genomics, Mendelian, Tan, Tiong Yang, Jiang, Yunyun, Gibbs, Richard A., Ellingwood, Sara, Amaral, Michelle, Kelley, Whitley, Kurian, Manju A., Cousin, Michael A., Raymond, F. Lucy, Zollino, Marcella (ORCID:0000-0003-4871-9519), Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Baker, Kate, Gordon, Sarah L., Melland, Holly, Bumbak, Fabian, Scott, Daniel J., Jiang, Tess J., Owen, David, Turner, Bradley J., Boyd, Stewart G., Rossi, Mari, Al-Raqad, Mohammed, Elpeleg, Orly, Peck, Dawn, Mancini, Grazia M. S., Wilke, Martina, Zollino, Marcella, Marangi, Giuseppe, Weigand, Heike, Borggraefe, Ingo, Haack, Tobia, Stark, Zornitza, Sadedin, Simon, Genomics, Mendelian, Tan, Tiong Yang, Jiang, Yunyun, Gibbs, Richard A., Ellingwood, Sara, Amaral, Michelle, Kelley, Whitley, Kurian, Manju A., Cousin, Michael A., Raymond, F. Lucy, Zollino, Marcella (ORCID:0000-0003-4871-9519), and Marangi, Giuseppe (ORCID:0000-0002-6898-8882)

Abstract

Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium-dependent neurotransmitter release and also modulates synaptic vesicle endocytosis. This paper describes 11 patients with de novo heterozygous missense mutations in SYT1. All mutations alter highly conserved residues, and cluster in two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G), Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. Behavioural characteristics include sleep disturbance and episodic agitation. Absence of epileptic seizures and normal orbitofrontal head circumference are important negative features. Structural MRI is unremarkable but EEG disturbance is universal, characterized by intermittent low frequency high amplitude oscillations. The functional impact of these five de novo SYT1 mutations has been assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest, except for SYT1M303K, which was expressed at a lower level and failed to localize at nerve terminals. Following stimulation, SYT1 I368T and SYT1 N371K relocalized to nerve terminals at least as efficiently as wild-type SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals following stimulation, indicative of impairments in endocytic retrieval and trafficking of SYT1. In addition, the presence of SYT1 variants at nerve terminals induced a slowing of exocytic rate following sustained action potential stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored by the severity of the affected individuals' phen

Published
2018

47. A novel truncating variant within exon 7 of KAT6B associated with features of both Sayâ€'Barberâ€'Biesekerâ€'Youngâ€'Simpson syndrome and genitopatellar syndrome: Further evidence of a continuum in the clinical spectrum of KAT6B-related disorders

Author

Marangi, Giuseppe, Di Giacomo, Marilena Carmela, Lattante, Serena, Orteschi, Daniela, Patrizi, Sara, Doronzio, Paolo N., Riviello, Francesco Nicola, Vaisfeld, Alessandro, Frangella, Silvia, Zollino, Marcella, Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Lattante, Serena (ORCID:0000-0003-2891-0340), Zollino, Marcella (ORCID:0000-0003-4871-9519), Marangi, Giuseppe, Di Giacomo, Marilena Carmela, Lattante, Serena, Orteschi, Daniela, Patrizi, Sara, Doronzio, Paolo N., Riviello, Francesco Nicola, Vaisfeld, Alessandro, Frangella, Silvia, Zollino, Marcella, Marangi, Giuseppe (ORCID:0000-0002-6898-8882), Lattante, Serena (ORCID:0000-0003-2891-0340), and Zollino, Marcella (ORCID:0000-0003-4871-9519)

Abstract

KAT6B sequence variants have been identified in both patients with the Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16–18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant-negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders with distinctive genetic and clinical features, there is evidence that they represent two ends of a spectrum of conditions referable as KAT6B-related disorders. We detected a de novo truncating variant within exon 7 of KAT6B in a 8-year-old female who presented with mild intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and skeletal anomalies including exostosis, that are usually considered component manifestations of GPS. Following the clinical diagnosis driven by the striking facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders.

Published
2018

49. Analysis of STMN2 CA repeats in italian ALS patients shows no association.

Author

Doronzio, Paolo Niccolò, Lattante, Serena, Marangi, Giuseppe, Martello, Francesco, Conte, Amelia, Bisogni, Giulia, Bernardo, Daniela, Patanella, Agata Katia, Meleo, Emiliana, Zollino, Marcella, and Sabatelli, Mario

Subjects
AMYOTROPHIC lateral sclerosis, NEURODEGENERATION
Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by a complex interaction of genetic and environmental factors. Recently, a polymorphic intronic CA repeat in STMN2 gene has been proposed as risk factor for ALS. The presence of long/long CA genotype, especially if one allele had 24 CA, was reported to be significantly associated with the disease in a cohort of sporadic ALS patients. We tested an Italian cohort of 366 ALS patients and 353 healthy controls and we found no association between CA length and ALS risk. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

50. High-throughput genetic testing in ALS: The challenging path of variant classification considering the acmg guidelines

Author

Lattante, Serena, Marangi, Giuseppe, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Zollino, Marcella, Sabatelli, Mario, Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Doronzio P. N., Zollino M. (ORCID:0000-0003-4871-9519), Sabatelli M. (ORCID:0000-0001-6635-4985), Lattante, Serena, Marangi, Giuseppe, Doronzio, Paolo Niccolo', Conte, A., Bisogni, G., Zollino, Marcella, Sabatelli, Mario, Lattante S. (ORCID:0000-0003-2891-0340), Marangi G. (ORCID:0000-0002-6898-8882), Doronzio P. N., Zollino M. (ORCID:0000-0003-4871-9519), and Sabatelli M. (ORCID:0000-0001-6635-4985)

Abstract

The development of high-throughput sequencing technologies and screening of big patient cohorts with familial and sporadic amyotrophic lateral sclerosis (ALS) led to the identification of a significant number of genetic variants, which are sometimes difficult to interpret. The American College of Medical Genetics and Genomics (ACMG) provided guidelines to help molecular geneticists and pathologists to interpret variants found in laboratory testing. We assessed the application of the ACMG criteria to ALS-related variants, combining data from literature with our experience. We analyzed a cohort of 498 ALS patients using massive parallel sequencing of ALS-associated genes and identified 280 variants with a minor allele frequency < 1%. Examining all variants using the ACMG criteria, thus considering the type of variant, inheritance, familial segregation, and possible functional studies, we classified 20 variants as “pathogenic”. In conclusion, ALS’s genetic complexity, such as oligogenic inheritance, presence of genes acting as risk factors, and reduced penetrance, needs to be considered when interpreting variants. The goal of this work is to provide helpful suggestions to geneticists and clinicians dealing with ALS.

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results