International Journal of Molecular Sciences (Aug 2021)
NGS in Hereditary Ataxia: When Rare Becomes Frequent
- Daniele Galatolo,
- Giovanna De Michele,
- Gabriella Silvestri,
- Vincenzo Leuzzi,
- Carlo Casali,
- Olimpia Musumeci,
- Antonella Antenora,
- Guja Astrea,
- Melissa Barghigiani,
- Roberta Battini,
- Carla Battisti,
- Caterina Caputi,
- Ettore Cioffi,
- Giuseppe De Michele,
- Maria Teresa Dotti,
- Tommasina Fico,
- Chiara Fiorillo,
- Serena Galosi,
- Maria Lieto,
- Alessandro Malandrini,
- Marina A. B. Melone,
- Andrea Mignarri,
- Gemma Natale,
- Elena Pegoraro,
- Antonio Petrucci,
- Ivana Ricca,
- Vittorio Riso,
- Salvatore Rossi,
- Anna Rubegni,
- Arianna Scarlatti,
- Francesca Tinelli,
- Rosanna Trovato,
- Gioacchino Tedeschi,
- Alessandra Tessa,
- Alessandro Filla,
- Filippo Maria Santorelli
Affiliations
- Daniele Galatolo
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Giovanna De Michele
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- Gabriella Silvestri
- UOC Neurologia, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, 00168 Rome, Italy
- Vincenzo Leuzzi
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy
- Carlo Casali
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 40100 Latina, Italy
- Olimpia Musumeci
- Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
- Antonella Antenora
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- Guja Astrea
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Melissa Barghigiani
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Roberta Battini
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Carla Battisti
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
- Caterina Caputi
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy
- Ettore Cioffi
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, 40100 Latina, Italy
- Giuseppe De Michele
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- Maria Teresa Dotti
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
- Tommasina Fico
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- Chiara Fiorillo
- Paediatric Neurology and Muscular Diseases Unit, University of Genoa and ‘G. Gaslini’ Institute, 16147 Genoa, Italy
- Serena Galosi
- Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy
- Maria Lieto
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- Alessandro Malandrini
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
- Marina A. B. Melone
- Center for Rare Diseases and Interuniversity Center for Research in Neurosciences, Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
- Andrea Mignarri
- Department of Medicine, Surgery and Neurosciences, University of Siena, 53100 Siena, Italy
- Gemma Natale
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Elena Pegoraro
- Department of Neurosciences, University of Padua, 35121 Padua, Italy
- Antonio Petrucci
- Azienda Ospedaliera San Camillo-Forlanini, 00152 Rome, Italy
- Ivana Ricca
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Vittorio Riso
- UOC Neurologia, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, 00168 Rome, Italy
- Salvatore Rossi
- UOC Neurologia, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, 00168 Rome, Italy
- Anna Rubegni
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Arianna Scarlatti
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Francesca Tinelli
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Rosanna Trovato
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Gioacchino Tedeschi
- Center for Rare Diseases and Interuniversity Center for Research in Neurosciences, Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy
- Alessandra Tessa
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- Alessandro Filla
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy
- Filippo Maria Santorelli
- Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy
- DOI
- https://doi.org/10.3390/ijms22168490
- Journal volume & issue
-
Vol. 22,
no. 16
p. 8490
Abstract
The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia-dominated phenotypes. Massive gene analysis in next-generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP-based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.
Keywords
