title: Motor chip: a comparative genomic hybridization microarray for copy-number mutations in 245 neuromuscular disorders.
abstract: 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: Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Naples, Italy.
authors: Giulio
authors: G
authors: Piluso
authors: Manuela
authors: M
authors: Dionisi
authors: Francesca
authors: F
authors: Del Vecchio Blanco
authors: Annalaura
authors: A
authors: Torella
authors: Stefania
authors: S
authors: Aurino
authors: Marco
authors: M
authors: Savarese
authors: Teresa
authors: T
authors: Giugliano
authors: Enrico
authors: E
authors: Bertini
authors: Alessandra
authors: A
authors: Terracciano
authors: Mariz
authors: M
authors: Vainzof
authors: Chiara
authors: C
authors: Criscuolo
authors: Luisa
authors: L
authors: Politano
authors: Carlo
authors: C
authors: Casali
authors: Filippo Maria
authors: FM
authors: Santorelli
authors: Vincenzo
authors: V
authors: Nigro
mesh_terms: D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004311:Double-Blind Method; D020440:Gene Duplication; D056726:Genetic Association Studies; D006801:Humans; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics; D009154:Mutation; D009468:Neuromuscular Diseases / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D049031:Sarcoglycans / Q000235:genetics; D017384:Sequence Deletion
chemical_list: C526573:SGCG protein, human; D049031:Sarcoglycans