title: Copy-number variations are enriched for neurodevelopmental genes in children with developmental coordination disorder.
abstract: 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.
  
  
  
  This study aims to investigate how CNVs may contribute to the genetic architecture of DCD.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mosca
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Lisa Marie
authors.initials: LM
authors.lastname: Langevin
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.|Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewey
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: A Micheil
authors.initials: AM
authors.lastname: Innes
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Molecular Genetics, McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anath C
authors.initials: AC
authors.lastname: Lionel
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Molecular Genetics, McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Marshall
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Molecular Genetics, McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.|Genetic Laboratory Services, Alberta Health Services, Calgary, Alberta, Canada.
authors.forename: Jillian S
authors.initials: JS
authors.lastname: Parboosingh
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada.|Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Francois P
authors.initials: FP
authors.lastname: Bernier
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D019957:Motor Skills Disorders / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D000072260:RNA Splicing Factors / Q000235:genetics; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D019922:GAP-43 Protein; D009419:Nerve Tissue Proteins; C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; C492357:SHANK3 protein, human; C102889:PTPRN2 protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8
keywords: Copy-number; Genome-wide; Neurosciences; Psychiatry