Abstract
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 namedMotorPlex 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.
| Original language | English |
|---|---|
| Pages (from-to) | 71-76 |
| Number of pages | 6 |
| Journal | Neurology |
| Volume | 87 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 5 2016 |
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ASJC Scopus subject areas
- Clinical Neurology
Cite this
The genetic basis of undiagnosed muscular dystrophies and myopathies. / Savarese, Marco; Di Fruscio, Giuseppina; Torella, Annalaura; Fiorillo, Chiara; Magri, Francesca; Fanin, Marina; Ruggiero, Lucia; Ricci, Giulia; Astrea, Guja; Passamano, Luigia; Ruggieri, Alessandra; Ronchi, Dario; Tasca, Giorgio; D'Amico, Adele; Janssens, Sandra; Farina, Olimpia; Mutarelli, Margherita; Marwah, Veer Singh; Garofalo, Arcomaria; Giugliano, Teresa; Sanpaolo, Simone; Del Vecchio Blanco, Francesca; Esposito, Gaia; Piluso, Giulio; D'Ambrosio, Paola; Petillo, Roberta; Musumeci, Olimpia; Rodolico, Carmelo; Messina, Sonia; Evilä, Anni; Hackman, Peter; Filosto, Massimiliano; Di Iorio, Giuseppe; Siciliano, Gabriele; Mora, Marina; Maggi, Lorenzo; Minetti, Carlo; Sacconi, Sabrina; Santoro, Lucio; Claes, Kathleen; Vercelli, Liliana; Mongini, Tiziana; Ricci, Enzo; Gualandi, Francesca; Tupler, Rossella; De Bleecker, Jan; Udd, Bjarne; Toscano, Antonio; Moggio, Maurizio; Pegoraro, Elena; Bertini, Enrico; Mercuri, Eugenio; Angelini, Corrado; Santorelli, Filippo Maria; Politano, Luisa; Bruno, Claudio; Comi, Giacomo Pietro; Nigro, Vincenzo.
In: Neurology, Vol. 87, No. 1, 05.07.2016, p. 71-76.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The genetic basis of undiagnosed muscular dystrophies and myopathies
AU - Savarese, Marco
AU - Di Fruscio, Giuseppina
AU - Torella, Annalaura
AU - Fiorillo, Chiara
AU - Magri, Francesca
AU - Fanin, Marina
AU - Ruggiero, Lucia
AU - Ricci, Giulia
AU - Astrea, Guja
AU - Passamano, Luigia
AU - Ruggieri, Alessandra
AU - Ronchi, Dario
AU - Tasca, Giorgio
AU - D'Amico, Adele
AU - Janssens, Sandra
AU - Farina, Olimpia
AU - Mutarelli, Margherita
AU - Marwah, Veer Singh
AU - Garofalo, Arcomaria
AU - Giugliano, Teresa
AU - Sanpaolo, Simone
AU - Del Vecchio Blanco, Francesca
AU - Esposito, Gaia
AU - Piluso, Giulio
AU - D'Ambrosio, Paola
AU - Petillo, Roberta
AU - Musumeci, Olimpia
AU - Rodolico, Carmelo
AU - Messina, Sonia
AU - Evilä, Anni
AU - Hackman, Peter
AU - Filosto, Massimiliano
AU - Di Iorio, Giuseppe
AU - Siciliano, Gabriele
AU - Mora, Marina
AU - Maggi, Lorenzo
AU - Minetti, Carlo
AU - Sacconi, Sabrina
AU - Santoro, Lucio
AU - Claes, Kathleen
AU - Vercelli, Liliana
AU - Mongini, Tiziana
AU - Ricci, Enzo
AU - Gualandi, Francesca
AU - Tupler, Rossella
AU - De Bleecker, Jan
AU - Udd, Bjarne
AU - Toscano, Antonio
AU - Moggio, Maurizio
AU - Pegoraro, Elena
AU - Bertini, Enrico
AU - Mercuri, Eugenio
AU - Angelini, Corrado
AU - Santorelli, Filippo Maria
AU - Politano, Luisa
AU - Bruno, Claudio
AU - Comi, Giacomo Pietro
AU - Nigro, Vincenzo
PY - 2016/7/5
Y1 - 2016/7/5
N2 - 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 namedMotorPlex 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.
AB - 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 namedMotorPlex 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.
UR - http://www.scopus.com/inward/record.url?scp=84977469403&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977469403&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000002800
DO - 10.1212/WNL.0000000000002800
M3 - Article
AN - SCOPUS:84977469403
VL - 87
SP - 71
EP - 76
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 1
ER -