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: Giulio Piluso, Manuela Dionisi, Francesca Del Vecchio Blanco, Annalaura Torella, Stefania Aurino, Marco Savarese, Teresa Giugliano, Enrico Bertini, Alessandra Terracciano, Mariz Vainzof, Chiara Criscuolo, Luisa Politano, Carlo Casali, Filippo Maria Santorelli, Vincenzo Nigro
• Journal: Clinical chemistry (Clin Chem) Vol. 57 Issue 11 Pg. 1584-96 (Nov 2011) ISSN: 1530-8561 [Electronic] England
• PMID: 21896784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SGCG protein, human
• Sarcoglycans

Topics

• Comparative Genomic Hybridization
• DNA Copy Number Variations
• Double-Blind Method
• Gene Duplication
• Genetic Association Studies
• Humans
• Muscular Dystrophies, Limb-Girdle (genetics)
• Mutation
• Neuromuscular Diseases (genetics)
• Oligonucleotide Array Sequence Analysis
• Sarcoglycans (genetics)
• Sequence Deletion