Abstract
BACKGROUND: Neurodevelopmental disorders are impairments of brain function that affect emotion, learning, and memory. Copy number variations of contactin genes (CNTNs), including CNTN3, CNTN4, CNTN5, and CNTN6, have been suggested to be associated with these disorders. However, phenotypes have been reported in only a handful of patients with copy number variations involving CNTNs. METHODS: From January 2009 to January 2013, 3724 patients ascertained through the University of Pittsburgh Medical Center were referred to our laboratory for clinical array comparative genomic hybridization testing. We screened this cohort of patients to identify individuals with the 3p26.3 copy number variations involving the CNTN6 gene, and then retrospectively reviewed the clinical information and family history of these patients to determine the association between the 3p26.3 copy number variations and neurodevelopmental disorders. RESULTS: Fourteen of the 3724 patients had 3p26.3 copy number variations involving the CNTN6 gene. Thirteen of the 14 patients with these CNTN6 copy number variations presented with various neurodevelopmental disorders including developmental delay, autistic spectrum disorders, seizures and attention deficit hyperactivity disorder. Family history was available for 13 of the 14 patients. Twelve of the thirteen families have multiple members with neurodevelopmental and neuropsychiatric disorders including attention deficit hyperactivity disorder, seizures, autism spectrum disorder, intellectual disability, schizophrenia, depression, anxiety, learning disability, and bipolar disorder. CONCLUSIONS: Our findings suggest that deletion or duplication of the CNTN6 gene is associated with a wide spectrum of neurodevelopmental behavioral disorders.