Williams, C.A. et al. Angelman syndrome 2005: updated consensus for diagnostic criteria. Am. J. Med. Genet. A. 140, 413-418

ArticleinAmerican Journal of Medical Genetics Part A 140(5):413-8 · March 2006with15 Reads
DOI: 10.1002/ajmg.a.31074 · Source: PubMed
In 1995, a consensus statement was published for the purpose of summarizing the salient clinical features of Angelman syndrome (AS) to assist the clinician in making a timely and accurate diagnosis. Considering the scientific advances made in the last 10 years, it is necessary now to review the validity of the original consensus criteria. As in the original consensus project, the methodology used for this review was to convene a group of scientists and clinicians, with experience in AS, to develop a concise consensus statement, supported by scientific publications where appropriate. It is hoped that this revised consensus document will facilitate further clinical study of individuals with proven AS, and assist in the evaluation of those who appear to have clinical features of AS but have normal laboratory diagnostic testing.
    • "Angelman syndrome (AS) is a debilitating neurodevelopmental disorder defined by severe developmental delay, movement disorders , profound speech impairment, and highly penetrant electroencephalographic (EEG) abnormalities and seizures (Williams et al., 2006; Thibert et al., 2013). The frequency, severity, and intractability of the seizures exact a heavy toll on the quality of life of individuals with AS and their caregivers (Thibert et al., 2013). "
    [Show abstract] [Hide abstract] ABSTRACT: Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs)-all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS.
    Full-text · Article · Mar 2016
    • "Further identification of such E3 ubiquitin ligases and their linked pathways implicated in the pathogenesis of protein conformational disorders will improve our understanding and open near-term prospects for therapeutics to a number of neurodegenerative diseases. Ube3a gene encodes an E3 ubiquitin ligase E6-Assoicated Protein (E6-AP) and mutations in this gene cause Angelman mental retardation syndrome, which is characterized by abnormal gait, tremor, ataxia, neurological impairment, deficits in expressive lan-guage and frequent laughter (Kishino et al., 1997; Lossie et al., 2001; Williams et al., 2006). Ube3a gene is localized at chromosome 15q11−13 region and maternal deletion of this region causes near about 70% cases of Angelman syndrome (AS) (Knoll et al., 1989). "
    [Show abstract] [Hide abstract] ABSTRACT: Efficient and regular performance of Ubiquitin Proteasome System and Autophagy continuously eliminate deleterious accumulation of nonnative protiens. In cellular quality control system, E3 ubiquitin ligases are significant employees for defense mechanism against abnormal toxic proteins. Few findings indicate that lack of functions of E3 ubiquitin ligases can be a causative factor of neurodevelopmental disorders, neurodegeneration, cancer and ageing. However, the detailed molecular pathomechanism implying E3 ubiquitin ligases in cellular functions in multifactorial disease conditions are not well understood. This article systematically represents the unique characteristics, molecular nature, and recent developments in the knowledge of neurobiological functions of few crucial E3 ubiquitin ligases. Here, we review recent literature on the roles of E6-AP, HRD1 and ITCH E3 ubiquitin ligases in the neuro-pathobiological mechanisms, with precise focus on the processes of neurodegeneration, and thereby propose new lines of potential targets for therapeutic interventions. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Aug 2015
    • "Angelman syndrome (AS) is a neuro-genetic disorder caused by disruption of the imprinted and maternally expressed UBE3A gene that occurs in approximately 1 : 12 000 live births (Steffenburg et al., 1996) and currently has no approved treatment. Children with this disorder present with developmental delay, severe speech impairment , ataxia, happy demeanor, and high seizure propensity (Williams et al., 2006). The AS mouse model was created by a null mutation of UBE3A, resulting in synaptic dysfunction and disruption in spatial and associative memory formation (Jiang et al., 1998). "
    [Show abstract] [Hide abstract] ABSTRACT: The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
    Full-text · Article · Apr 2015
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