TY - JOUR
T1 - Motor chip
T2 - A comparative genomic hybridization microarray for copy-number mutations in 245 neuromuscular disorders
AU - Piluso, Giulio
AU - Dionisi, Manuela
AU - Blanco, Francesca Del Vecchio
AU - Torella, Annalaura
AU - Aurino, Stefania
AU - Savarese, Marco
AU - Giugliano, Teresa
AU - Bertini, Enrico
AU - Terracciano, Alessandra
AU - Vainzof, Mariz
AU - Criscuolo, Chiara
AU - Politano, Luisa
AU - Casali, Carlo
AU - Santorelli, Filippo Maria
AU - Nigro, Vincenzo
PY - 2011/11
Y1 - 2011/11
N2 - 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: Wedeveloped 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 dystrophinassociated 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.
AB - 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: Wedeveloped 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 dystrophinassociated 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.
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U2 - 10.1373/clinchem.2011.168898
DO - 10.1373/clinchem.2011.168898
M3 - Article
C2 - 21896784
AN - SCOPUS:80055068583
VL - 57
SP - 1584
EP - 1596
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 11
ER -