Clinically relevant copy number variations detected in cerebral palsy

• Published in: Nature communications Vol. 6; no. 1; p. 7949
• Main Authors: Oskoui, Maryam, Gazzellone, Matthew J., Thiruvahindrapuram, Bhooma, Zarrei, Mehdi, Andersen, John, Wei, John, Wang, Zhuozhi, Wintle, Richard F., Marshall, Christian R., Cohn, Ronald D., Weksberg, Rosanna, Stavropoulos, Dimitri J., Fehlings, Darcy, Shevell, Michael I., Scherer, Stephen W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.08.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 631/208/457/649/2157; 692/699/375/2764; Abnormalities; Brain damage; Brain injury; Case-Control Studies; Cerebral palsy; Cerebral Palsy - genetics; Children; Chromosome Aberrations; Chromosomes, Human - genetics; Cohort Studies; Copy number; Damage assessment; Diagnostic systems; Disorders; DNA Copy Number Variations - genetics; Environmental stress; Female; Genetic screening; Genotype; Genotypes; Health risk assessment; Humanities and Social Sciences; Humans; Male; multidisciplinary; Neurodevelopmental disorders; Paralysis; Parents; Prospective Studies; Risk analysis; Risk factors; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8949

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. Cerebral palsy (CP) is a heterogeneous disorder that has been historically attributed to environmental factors with genetic contributions being discovered more recently. Here the authors perform microarray-based analysis of copy number variations in a cohort of children with CP and their parents and find chromosomal abnormalities linked to the disease.