title: Clinically relevant copy number variations detected in cerebral palsy.
abstract: Cerebral palsy (CP) represents a group of non-progressive clinically heterogeneous disorders that are characterized by motor impairment and early age of onset, frequently accompanied by co-morbidities. The cause of CP has historically been attributed to environmental stressors resulting in brain damage. While genetic risk factors are also implicated, guidelines for diagnostic assessment of CP do not recommend for routine genetic testing. Given numerous reports of aetiologic copy number variations (CNVs) in other neurodevelopmental disorders, we used microarrays to genotype a population-based prospective cohort of children with CP and their parents. Here we identify de novo CNVs in 8/115 (7.0%) CP patients (∼1% rate in controls). In four children, large chromosomal abnormalities deemed likely pathogenic were found, and they were significantly more likely to have severe neuromotor impairments than those CP subjects without such alterations. Overall, the CNV data would have impacted our diagnosis or classification of CP in 11/115 (9.6%) families.
authors.affiliation: Departments of Pediatrics and Neurology/Neurosurgery, McGill University, Montreal, Quebec, Canada H3H 1P3.
authors.forename: Maryam
authors.initials: M
authors.lastname: Oskoui
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gazzellone
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Bhooma
authors.initials: B
authors.lastname: Thiruvahindrapuram
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Zarrei
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta Canada T6G 2B7.|Glenrose Rehabilitation Hospital, Edmonton, Alberta, Canada T5G 0B7.
authors.forename: John
authors.initials: J
authors.lastname: Andersen
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: John
authors.initials: J
authors.lastname: Wei
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Zhuozhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Wintle
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Genome Diagnostics, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada M5G 1X8.|Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.|Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Cohn
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada M5G 1X8.|Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.affiliation: Genome Diagnostics, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.|Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Dimitri J
authors.initials: DJ
authors.lastname: Stavropoulos
authors.affiliation: Holland Bloorview Kids Rehabilitation Hospital, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada M4G 1R8.
authors.forename: Darcy
authors.initials: D
authors.lastname: Fehlings
authors.affiliation: Departments of Pediatrics and Neurology/Neurosurgery, McGill University, Montreal, Quebec, Canada H3H 1P3.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Shevell
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 0A4.|Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.|Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
mesh_terms: D016022:Case-Control Studies; D002547:Cerebral Palsy / Q000235:genetics*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010290:Parents; D011446:Prospective Studies