Clinically Relevant Copy Number Variations Detected in Cerebral Palsy

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 etiologic 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 pathogenic were found, and they were significantly more likely to have severe neuro-motor 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. Dr. Maryam Oskoui* , Mr. Matthew Gazzellone* , Ms. Bhooma Thiruvahindrapuram , Dr. Mehdi Zarrei , Dr. John Andersen , Dr. John Wei , Dr. Zhouzhi Wang , Dr. Richard Wintle , Dr. Christian Marshall , Dr. Ronald Cohn , Dr. Rosanna Weksberg , Dr. James Stavropoulos , Dr. Darcy Fehlings , Dr. Michael Shevell, Dr. Stephen Scherer. Clinically Relevant Copy Number Variations Detected in Cerebral Palsy. Nature Communications, 2015. Following our rigorous quality control procedure, we successfully genotyped 147 proband samples from individuals with cerebral palsy (81 males and 66 females) and 282 samples obtained from parents (134 males and 148 females). This facilitated the identification of de novo and rare inherited copy number variations of clinical interest.