The genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients.
Savarese, Marco PhD; Di Fruscio, Giuseppina PhD; Torella, Annalaura PhD; Fiorillo, Chiara MD; Magri, Francesca MD; Fanin, Marina PhD; Ruggiero, Lucia MD; Ricci, Giulia MD; Astrea, Guja PhD; Passamano, Luigia MD; Ruggieri, Alessandra PhD; Ronchi, Dario PhD; Tasca, Giorgio MD; D'Amico, Adele MD; Janssens, Sandra MD; Farina, Olimpia MD; Mutarelli, Margherita PhD; Marwah, Veer Singh MSc; Garofalo, Arcomaria MSc; Giugliano, Teresa PhD; Sanpaolo, Simone MD; Del Vecchio Blanco, Francesca PhD; Esposito, Gaia BSc; Piluso, Giulio PhD; D'Ambrosio, Paola MD; Petillo, Roberta MD; Musumeci, Olimpia MD; Rodolico, Carmelo MD; Messina, Sonia MD; Evila, Anni PhD; Hackman, Peter PhD; Filosto, Massimiliano MD; Di Iorio, Giuseppe MD; Siciliano, Gabriele MD; Mora, Marina PhD; Maggi, Lorenzo MD; Minetti, Carlo MD; Sacconi, Sabrina MD; Santoro, Lucio MD; Claes, Kathleen PhD; Vercelli, Liliana MD; Mongini, Tiziana MD; Ricci, Enzo MD; Gualandi, Francesca MD; Tupler, Rossella MD; De Bleecker, Jan MD; Udd, Bjarne MD; Toscano, Antonio MD; Moggio, Maurizio MD; Pegoraro, Elena MD; Bertini, Enrico MD; Mercuri, Eugenio MD; Angelini, Corrado MD; Santorelli, Filippo Maria MD; Politano, Luisa MD; Bruno, Claudio MD; Comi, Giacomo Pietro MD; Nigro, Vincenzo MD
87(1):71-76, July 05, 2016.
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Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients.
Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy.
Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes.
Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions.
(C) 2016 American Academy of Neurology