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Copy-number variation
Original article
Copy-number variations are enriched for neurodevelopmental genes in children with developmental coordination disorder
  1. Stephen J Mosca1,
  2. Lisa Marie Langevin2,
  3. Deborah Dewey2,3,4,
  4. A Micheil Innes1,2,
  5. Anath C Lionel5,6,
  6. Christian C Marshall5,6,
  7. Stephen W Scherer5,6,
  8. Jillian S Parboosingh1,2,7,
  9. Francois P Bernier1,2
  1. 1Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
  2. 2Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
  3. 3Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
  4. 4Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
  5. 5The Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada
  6. 6Department of Molecular Genetics, McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada
  7. 7Genetic Laboratory Services, Alberta Health Services, Calgary, Alberta, Canada
  1. Correspondence to Dr Francois P Bernier, Department of Medical Genetics, Faculty of Medicine, University of Calgary, 2888 Shaganappi Trail NW, Calgary, Alberta, Canada T3B6A8; francois.bernier{at}albertahealthservices.ca

Abstract

Background Developmental coordination disorder is a common neurodevelopment disorder that frequently co-occurs with other neurodevelopmental disorders including attention-deficit hyperactivity disorder (ADHD). Copy-number variations (CNVs) have been implicated in a number of neurodevelopmental and psychiatric disorders; however, the proportion of heritability in developmental coordination disorder (DCD) attributed to CNVs has not been explored.

Objective This study aims to investigate how CNVs may contribute to the genetic architecture of DCD.

Methods CNV analysis was performed on 82 extensively phenotyped Canadian children with DCD, with or without co-occurring ADHD and/or reading disorder, and 2988 healthy European controls using identical genome-wide SNP microarrays and CNV calling algorithms.

Results An increased rate of large and rare genic CNVs (p=0.009) was detected, and there was an enrichment of duplications spanning brain-expressed genes (p=0.039) and genes previously implicated in other neurodevelopmental disorders (p=0.043). Genes and loci of particular interest in this group included: GAP43, RBFOX1, PTPRN2, SHANK3, 16p11.2 and distal 22q11.2. Although no recurrent CNVs were identified, 26% of DCD cases, where sample availability permitted segregation analysis, were found to have a de novo rare CNV. Of the inherited CNVs, 64% were from a parent who also had a neurodevelopmental disorder.

Conclusions These findings suggest that there may be shared susceptibility genes for DCD and other neurodevelopmental disorders and highlight the need for thorough phenotyping when investigating the genetics of neurodevelopmental disorders. Furthermore, these data provide compelling evidence supporting a genetic basis for DCD, and further implicate rare CNVs in the aetiology of neurodevelopmental disorders.

  • Genome-wide
  • Neurosciences
  • Copy-number
  • Psychiatry

https://doi.org/10.1136/jmedgenet-2016-103818

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    Footnotes

    • Contributors FPB reviewed the suggested guidelines for authorship and confirmed each of the authors meet all four of the suggested criteria for authorship.

    • Funding Institute of Human Development, Child and Youth Health (MOP-86588).

    • Competing interests None declared.

    • Ethics approval Conjoint Medical Health Research Committee – University of Calgary.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Currently, unpublished raw SNP array data have not been shared in public database and remain the intellectual property of the investigators. The authors do favour data sharing and will endeavour to do once our research on the CNVs and DCD is completed.