title: 15q11.2 Duplication Encompassing Only the UBE3A Gene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes.
abstract: Duplications of chromosome region 15q11-q13 with the maternal imprint are associated with a wide spectrum of neuropsychiatric disorders, including autism spectrum disorders, developmental delay, learning difficulties, schizophrenia, and seizures. These observations suggest there is a dosage-sensitive imprinted gene or genes within this region that explains the increased risk for neuropsychiatric phenotypes. We present a female patient with developmental delay in whom we identified a maternally inherited 129-Kb duplication in chromosome region 15q11.2 encompassing only the UBE3A gene. Expression analysis in cultured fibroblasts confirmed overexpression of UBE3A in the proband, compared with age- and sex-matched controls. We further tested segregation of this duplication in four generations and found it segregated with neuropsychiatric phenotypes. Our study shows for the first time clinical features associated with overexpression of UBE3A in humans and underscores the significance of this gene in the phenotype of individuals with 15q11-q13 duplication.
authors.affiliation: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.|Pathology and Laboratory Medicine, Mount Sinai Hospital Joseph and Wolf Lebovic Health Complex, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Abdul
authors.initials: A
authors.lastname: Noor
authors.affiliation: The Hospital for Sick Children, Department of Pediatrics, Division of Clinical and Metabolic Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lucie
authors.initials: L
authors.lastname: Dupuis
authors.affiliation: Molecular Neuropsychiatry & Development Lab, The Campbell Family Brain Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Kirti
authors.initials: K
authors.lastname: Mittal
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Anath C
authors.initials: AC
authors.lastname: Lionel
authors.affiliation: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.|The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.|McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.|McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tracy
authors.initials: T
authors.lastname: Stockley
authors.affiliation: Molecular Neuropsychiatry & Development Lab, The Campbell Family Brain Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
authors.affiliation: The Hospital for Sick Children, Department of Pediatrics, Division of Clinical and Metabolic Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendoza-Londono
authors.affiliation: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dimitri J
authors.initials: DJ
authors.lastname: Stavropoulos
mesh_terms: D002884:Chromosomes, Human, Pair 15; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D020440:Gene Duplication; D056726:Genetic Association Studies; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics*; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: UBE3A; autism; copy-number variants; imprinting; neuropsychiatric