An Extended Targeted Copy Number Variation Detection Array Including 187 Genes for the Diagnostics of Neuromuscular Disorders

L. Sagath, V.-L. Lehtokari, S. Välipakka, B. Udd, C. Wallgren-Pettersson, K. Pelin, K. Kiiski

Research output: Contribution to journalArticleScientificpeer-review


Background: Our previous array, the Comparative Genomic Hybridisation design (CGH-array) for nemaline myopathy (NM), named the NM-CGH array, revealed pathogenic copy number variation (CNV) in the genes for nebulin (NEB) and tropomyosin 3 (TPM3), as well as recurrent CNVs in the segmental duplication (SD), i.e. triplicate, region of NEB (TRI, exons 82-89, 90-97, 98-105). In the light of this knowledge, we have designed and validated an extended CGH array, which includes a selection of 187 genes known to cause neuromuscular disorders (NMDs). Objective: Our aim was to develop a reliable method for CNV detection in genes related to neuromuscular disorders for routine mutation detection and analysis, as a much-needed complement to sequencing methods. Methods: We have developed a novel custom-made 4×180 k CGH array for the diagnostics of NMDs. It includes the same tiled ultra-high density coverage of the 12 known or putative NM genes as our 8×60 k NM-CGH-array but also comprises a selection of 175 additional genes associated with NMDs, including titin (TTN), at a high to very high coverage. The genes were divided into three coverage groups according to known and potential pathogenicity in neuromuscular disorders. Results: The array detected known and putative CNVs in all three gene coverage groups, including the repetitive regions of NEB and TTN. Conclusions: The targeted neuromuscular disorder 4×180 k array-CGH (NMD-CGH-array v1.0) design allows CNV detection for a broader spectrum of neuromuscular disorders at a high resolution. © 2018 - IOS Press and the authors. All rights reserved.
Original languageEnglish
JournalJournal of Neuromuscular Diseases
Issue number3
Pages (from-to)307-314
Number of pages8
Publication statusPublished - 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • connectin
  • DNA
  • muscle protein
  • nebulin
  • TTN protein, human, Article
  • clinical article
  • comparative genomic hybridization
  • controlled study
  • copy number variation
  • gene deletion
  • gene duplication
  • gene loss
  • genetic association
  • genetic gain
  • human
  • mutational analysis
  • NEB gene
  • neuromuscular disease
  • pathogenicity
  • priority journal
  • reliability
  • TTN gene
  • adult
  • DNA microarray
  • female
  • genetics
  • genomics
  • male
  • microarray analysis
  • mutation
  • nemaline myopathy
  • procedures
  • reproducibility, Adult
  • Connectin
  • DNA Copy Number Variations
  • Female
  • Genomics
  • Humans
  • Male
  • Microarray Analysis
  • Muscle Proteins
  • Mutation
  • Myopathies, Nemaline
  • Neuromuscular Diseases
  • Oligonucleotide Array Sequence Analysis
  • Reproducibility of Results
  • 1184 Genetics, developmental biology, physiology
  • 3112 Neurosciences
  • 3121 General medicine, internal medicine and other clinical medicine

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