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.
Keywords: UBE3A; autism; copy-number variants; imprinting; neuropsychiatric.
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