BACKGROUND: Array-based comparative genomic hybridization (aCGH) is a reference high-throughput technology for detecting large pathogenic or polymorphic copy-number variations in the human genome; however, a number of quantitative monogenic mutations, such as smaller heterozygous deletions or duplications, are usually missed in most disease genes when proper multiplex ligation-dependent probe assays are not performed. METHODS: We developed the Motor Chip, a customized CGH array with exonic coverage of 245 genes involved in neuromuscular disorders (NMDs), as well as 180 candidate disease genes. We analyzed DNA samples from 26 patients with known deletions or duplications in NMDs, 11 patients with partial molecular diagnoses, and 19 patients with a clinical diagnosis alone. RESULTS: The Motor Chip efficiently confirmed and refined the copy-number mutations in all of the characterized patients, even when only a single exon was involved. In noncharacterized or partially characterized patients, we found deletions in the SETX (senataxin), SGCG [sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein)], and LAMA2 (laminin, alpha 2) genes, as well as duplications involving LAMA2 and the DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)] locus. CONCLUSIONS: The combination of exon-specific gene coverage and optimized platform and probe selection makes the Motor Chip a complementary tool for molecular diagnosis and gene investigation in neuromuscular diseases.
BACKGROUND: Array-based comparative genomic hybridization (aCGH) is a reference high-throughput technology for detecting large pathogenic or polymorphic copy-number variations in the human genome; however, a number of quantitative monogenic mutations, such as smaller heterozygous deletions or duplications, are usually missed in most disease genes when proper multiplex ligation-dependent probe assays are not performed. METHODS: We developed the Motor Chip, a customized CGH array with exonic coverage of 245 genes involved in neuromuscular disorders (NMDs), as well as 180 candidate disease genes. We analyzed DNA samples from 26 patients with known deletions or duplications in NMDs, 11 patients with partial molecular diagnoses, and 19 patients with a clinical diagnosis alone. RESULTS: The Motor Chip efficiently confirmed and refined the copy-number mutations in all of the characterized patients, even when only a single exon was involved. In noncharacterized or partially characterized patients, we found deletions in the SETX (senataxin), SGCG [sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein)], and LAMA2 (laminin, alpha 2) genes, as well as duplications involving LAMA2 and the DYSF [dysferlin, limb girdle muscular dystrophy 2B (autosomal recessive)] locus. CONCLUSIONS: The combination of exon-specific gene coverage and optimized platform and probe selection makes the Motor Chip a complementary tool for molecular diagnosis and gene investigation in neuromuscular diseases.
Authors: Brent L Fogel; Ellen Cho; Amanda Wahnich; Fuying Gao; Olivier J Becherel; Xizhe Wang; Francesca Fike; Leslie Chen; Chiara Criscuolo; Giuseppe De Michele; Alessandro Filla; Abigail Collins; Angelika F Hahn; Richard A Gatti; Genevieve Konopka; Susan Perlman; Martin F Lavin; Daniel H Geschwind; Giovanni Coppola Journal: Hum Mol Genet Date: 2014-04-23 Impact factor: 6.150
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
Authors: Renate Marquis-Nicholson; Elaine Doherty; Jennifer M Love; Chuan-Ching Lan; Alice M George; Anthony Thrush; Donald R Love Journal: Sultan Qaboos Univ Med J Date: 2013-02-27
Authors: Marina Mora; Corrado Angelini; Fabrizia Bignami; Anne-Mary Bodin; Marco Crimi; Jeanne-Hélène Di Donato; Alex Felice; Cécile Jaeger; Veronika Karcagi; Yann LeCam; Stephen Lynn; Marija Meznaric; Maurizio Moggio; Lucia Monaco; Luisa Politano; Manuel Posada de la Paz; Safaa Saker; Peter Schneiderat; Monica Ensini; Barbara Garavaglia; David Gurwitz; Diana Johnson; Francesco Muntoni; Jack Puymirat; Mojgan Reza; Thomas Voit; Chiara Baldo; Franca Dagna Bricarelli; Stefano Goldwurm; Giuseppe Merla; Elena Pegoraro; Alessandra Renieri; Kurt Zatloukal; Mirella Filocamo; Hanns Lochmüller Journal: Eur J Hum Genet Date: 2014-12-24 Impact factor: 4.246