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.
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.
Authors: O Musumeci; G la Marca; M Spada; S Mondello; C Danesino; G P Comi; E Pegoraro; G Antonini; G Marrosu; R Liguori; L Morandi; M Moggio; R Massa; S Ravaglia; A Di Muzio; M Filosto; P Tonin; G Di Iorio; S Servidei; G Siciliano; C Angelini; T Mongini; A Toscano Journal: J Neurol Neurosurg Psychiatry Date: 2015-03-17 Impact factor: 10.154
Authors: Settara C Chandrasekharappa; Francis P Lach; Danielle C Kimble; Aparna Kamat; Jamie K Teer; Frank X Donovan; Elizabeth Flynn; Shurjo K Sen; Supawat Thongthip; Erica Sanborn; Agata Smogorzewska; Arleen D Auerbach; Elaine A Ostrander Journal: Blood Date: 2013-04-23 Impact factor: 22.113
Authors: G Piluso; L Politano; S Aurino; M Fanin; E Ricci; V M Ventriglia; A Belsito; A Totaro; V Saccone; H Topaloglu; A C Nascimbeni; L Fulizio; A Broccolini; N Canki-Klain; L I Comi; G Nigro; C Angelini; V Nigro Journal: J Med Genet Date: 2005-09 Impact factor: 6.318
Authors: Marco Savarese; Lorenzo Maggi; Anna Vihola; Per Harald Jonson; Giorgio Tasca; Lucia Ruggiero; Luca Bello; Francesca Magri; Teresa Giugliano; Annalaura Torella; Anni Evilä; Giuseppina Di Fruscio; Olivier Vanakker; Sara Gibertini; Liliana Vercelli; Alessandra Ruggieri; Carlo Antozzi; Helena Luque; Sandra Janssens; Maria Barbara Pasanisi; Chiara Fiorillo; Monika Raimondi; Manuela Ergoli; Luisa Politano; Claudio Bruno; Anna Rubegni; Marika Pane; Filippo M Santorelli; Carlo Minetti; Corrado Angelini; Jan De Bleecker; Maurizio Moggio; Tiziana Mongini; Giacomo Pietro Comi; Lucio Santoro; Eugenio Mercuri; Elena Pegoraro; Marina Mora; Peter Hackman; Bjarne Udd; Vincenzo Nigro Journal: JAMA Neurol Date: 2018-05-01 Impact factor: 18.302