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.
Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons
Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy
Methylation-specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences
Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions
Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders
Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice.
High frequency of known copy number abnormalities and maternal duplication 15q11-q13 in patients with combined schizophrenia and epilepsy.
Overexpression of chromosome 15q11-q13 gene products: a risk factor for schizophrenia and associated psychoses?
The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature
New discoveries in schizophrenia genetics reveal neurobiological pathways: A review of recent findings
New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain
Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders
Topoisomerase 1 Regulates Gene Expression in Neurons through Cleavage Complex-Dependent and -Independent Mechanisms
Maternally derived 15q11.2-q13.1 duplication and H19-DMR hypomethylation in a patient with Silver-Russell syndrome
The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/β-catenin pathway by inhibiting the proteasome.
Neuronal overexpression of Ube3a isoform 2 causes behavioral impairments and neuroanatomical pathology relevant to 15q11.2-q13.3 duplication syndrome
Angelman syndrome-associated point mutations in the Zn2+-binding N-terminal (AZUL) domain of UBE3A ubiquitin ligase inhibit binding to the proteasome.
Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders
Neuronal Proteomic Analysis of the Ubiquitinated Substrates of the Disease-Linked E3 Ligases Parkin and Ube3a
Hereditary Spastic Paraplegia and Intellectual Disability: Clinicogenetic Lessons From a Family Suggesting a Dual Genetics Diagnosis
High Incidence of Copy Number Variants in Adults with Intellectual Disability and Co-morbid Psychiatric Disorders
ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism
Quantitative proteomics reveals neuronal ubiquitination of Rngo/Ddi1 and several proteasomal subunits by Ube3a, accounting for the complexity of Angelman syndrome
The role of ubiquitin ligase E3A in polarized contact guidance and rescue strategies in UBE3A-deficient hippocampal neurons
Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders.
An alternative splicing hypothesis for neuropathology of schizophrenia: evidence from studies on historical candidate genes and multi-omics data.
Molecular Evolution, Neurodevelopmental Roles and Clinical Significance of HECT-Type UBE3 E3 Ubiquitin Ligases.
Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.