Copy number variants account for a tiny fraction of undiagnosed myopathic patients

Teresa Giugliano, Marco Savarese, Arcomaria Garofalo, Esther Picillo, Chiara Fiorillo, Adele D’amico, Lorenzo Maggi, Lucia Ruggiero, Liliana Vercelli, Francesca Magri, Fabiana Fattori, Annalaura Torella, Manuela Ergoli, Anna Rubegni, Marina Fanin, Olimpia Musumeci, Jan De Bleecker, Lorenzo Peverelli, Maurizio Moggio, Eugenio MercuriAntonio Toscano, Marina Mora, Lucio Santoro, Tiziana Mongini, Enrico Bertini, Claudio Bruno, Carlo Minetti, Giacomo Pietro Comi, Filippo Maria Santorelli, Corrado Angelini, Luisa Politano, Giulio Piluso, Vincenzo Nigro

Research output: Contribution to journalArticlepeer-review


Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5–9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.

Original languageEnglish
Article number524
Issue number11
Publication statusPublished - Nov 1 2018


  • Copy number variants
  • Next-generation sequencing
  • Skeletal muscle disorders
  • Variants of uncertain significance

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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