Copy number variants account for a tiny fraction of undiagnosed myopathic patients
| Autor: | Tiziana Mongini, Lorenzo Peverelli, Marina Mora, Esther Picillo, Adele D'Amico, Giulio Piluso, Lorenzo Maggi, Jan De Bleecker, Marco Savarese, Corrado Angelini, Luisa Politano, Filippo M. Santorelli, Annalaura Torella, Liliana Vercelli, Olimpia Musumeci, Carlo Minetti, Giacomo P. Comi, Eugenio Mercuri, Maurizio Moggio, Enrico Bertini, Francesca Magri, Lucia Ruggiero, Claudio Bruno, Fabiana Fattori, Manuela Ergoli, Chiara Fiorillo, Antonio Toscano, Vincenzo Nigro, Arcomaria Garofalo, Anna Rubegni, Lucio Santoro, Marina Fanin, Teresa Giugliano |
|---|---|
| Přispěvatelé: | Giugliano, Teresa, Savarese, Marco, Garofalo, Arcomaria, Picillo, Esther, Fiorillo, Chiara, D’Amico, Adele, Maggi, Lorenzo, Ruggiero, Lucia, Vercelli, Liliana, Magri, Francesca, Fattori, Fabiana, Torella, Annalaura, Ergoli, Manuela, Rubegni, Anna, Fanin, Marina, Musumeci, Olimpia, De Bleecker, Jan, Peverelli, Lorenzo, Moggio, Maurizio, Mercuri, Eugenio, Toscano, Antonio, Mora, Marina, Santoro, Lucio, Mongini, Tiziana, Bertini, Enrico, Bruno, Claudio, Minetti, Carlo, Comi, Giacomo Pietro, Santorelli, Filippo Maria, Angelini, Corrado, Politano, Luisa, Piluso, Giulio, Nigro, Vincenzo, Medicum, Teresa, Giugliano, Marco, Savarese, Arcomaria, Garofalo, Esther, Picillo, Chiara, Fiorillo, Adele, D’Amico, Lorenzo, Maggi, Lucia, Ruggiero, Liliana, Vercelli, Francesca, Magri, Fabiana, Fattori, Manuela, Ergoli, Anna, Rubegni, Marina, Fanin, Olimpia, Musumeci, Jan De Bleecker, Lorenzo, Peverelli, Maurizio, Moggio, Eugenio, Mercuri, Antonio, Toscano, Marina, Mora, Lucio, Santoro, Tiziana, Mongini, Enrico, Bertini, Claudio, Bruno, Carlo, Minetti, Giacomo Pietro Comi, Filippo Maria Santorelli, Corrado, Angelini |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities lcsh:QH426-470 MYOPATHIC PATIENTS Copy number variants Next-generation sequencing Skeletal muscle disorders Variants of uncertain significance Genetics Genetics (clinical) Disease skeletal muscle disorders Biology Copy number variant Article 03 medical and health sciences Settore MED/39 - NEUROPSICHIATRIA INFANTILE 0302 clinical medicine Genetic Gene duplication medicine Copy-number variation Multiplex ligation-dependent probe amplification Myopathy Gene Skeletal muscle disorder 1184 Genetics developmental biology physiology Phenotype 3. Good health lcsh:Genetics 030104 developmental biology medicine.symptom 030217 neurology & neurosurgery copy number variants Comparative genomic hybridization |
| Zdroj: | Genes Genes, Vol 9, Iss 11, p 524 (2018) Volume 9 Issue 11 |
| Popis: | 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&ndash 9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|