title: Orchestration of neurodevelopmental programs by RBFOX1: implications for autism spectrum disorder.
abstract: Neurodevelopmental and neuropsychiatric disorders result from complex interactions between critical genetic factors and as-yet-unknown environmental components. To gain clinical insight, it is critical to develop a comprehensive understanding of these genetic components. RBFOX1, an RNA splicing factor, regulates expression of large genetic networks during early neuronal development, and haploinsufficiency causes severe neurodevelopmental phenotypes including autism spectrum disorder (ASD), intellectual disability, and epilepsy. Genomic testing in individuals and large patient cohorts has identified phenotypically similar cases possessing copy number variations in RBFOX1, implicating the gene as an important cause of neurodevelopmental disease. However, a significant proportion of the observed structural variation is inherited from phenotypically normal individuals, raising questions regarding overall pathogenicity of variation at the RBFOX1 locus. In this chapter, we discuss the molecular, cellular, and clinical evidence supporting the role of RBFOX1 in neurodevelopment and present a comprehensive model for the contribution of structural variation in RBFOX1 to ASD.
authors.affiliation: Department of Psychiatry, David Geffen School of Medicine, Center for Autism Research and Treatment and Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, USA.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Bill
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lowe
authors.forename: Christina T
authors.initials: CT
authors.lastname: Dybuncio
authors.forename: Brent L
authors.initials: BL
authors.lastname: Fogel
mesh_terms: D000818:Animals; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D002658:Developmental Disabilities / Q000378:metabolism / Q000473:pathology*; D004827:Epilepsy / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins
keywords: A2BP1; Autism; Autism spectrum disorder; Copy number variation; FOX1; Neurodevelopment; RBFOX1; RNA splicing