DermKnowledgeBASE: Angelman Syndrome

Angelman Syndrome

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The text is the summary of recent articles on Angelman Syndrome at 75 thresold from National Library of Medicine (NLM). This information is subject to NCBI's Disclaimer and Copyright notice.


In AS, patients suffer from a more severe developmental delay, they have a distinctive behaviour that is often described as unnaturally happy, and a tendency for Epileptic seizures [1]. All duplications have encompassed the Prader Willi/Angelman syndrome critical region (PWACR) [2]. Similar gains in copy number were not detected among the parents of the patients,suggesting a de novo origin for them [3]. Characteristic features of AS includes developmental delay or intellectual disability, severe speech impairment, seizures, small Head size (microcephaly), and problems with movement and balance (ataxia) [4]. Defects in imprinting regulation (IE), uniparental disomy (UPD) or copy Number variation (CNV) due to chromosomal breakpoints (BP) in 15q11-q13 region, are associated with several diseases [5].

Males with CS typically present with global developmental delay, later meeting criteria for severe intellectual disability (ID) [6]. Here we employ touchscreen visual discrimination learning to evaluate performance in the maternally derived Ube3a mouse model of angelman syndrome, the Ts65Dn trisomy mouse model of Down Syndrome, and the Mecp2Bird mouse model of Rett syndrome [7]. Though his clinical profile and electroencephalogram were suggestive of angelman syndrome, initial genetic tests were unyielding [8]. Exome sequencing revealed a previously unreported mutation of Ubiquitin Protein Ligase E3A (UBE3A) gene, confirming the diagnosis of angelman syndrome [9]. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common [10].

Replacement of sex hormones at puberty produces adequate secondary sexual characteristics [11]. In adulthood, a group home for individuals with PWS that regulates behavior and weight management may prevent morbid obesity, and growth hormone may help to maintain Muscle bulk [12]. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples [13]. Although the obtained positive predictive values compare favorably with those seen in traditional screening approaches for common aneuploidies, they highlight the importance of educating clinicians and patients on the limitations of cell-free Fetal DNA screening tests [14]. Improvement of the cell-free Fetal DNA screening technology and continued monitoring of its performance after introduction into clinical practice will be important to fully establish its clinical utility [15].

The UBE3A gene demonstrates maternal-specific expression in neurons and loss of maternal UBE3A causes angelman syndrome, a neurodevelopmental disorder with some overlapping neurological features to Dup15q [16]. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation [17]. The rest are associated with point Mutations in the UBE3A gene, imprinting defects, and paternal uniparental disomy [18]. The authors decided to select eight relatively well-known neurogenetic disorders including Down Syndrome, angelman syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular Dystrophy [19]. We have shown that neuronal activity shifts the balance toward stabilization of Rnf2 through self-polyubiquitination rather than triggering its degradation through polyubiquitination by Ube3A, an E3 ligase implicated in angelman syndrome [20].

The information source for AS cases was the information system for rare diseases in the CM [21]. The immediate-early gene Arc, a master regulator of synaptic plasticity, was identified as a putative substrate of Ube3A, but there have been conflicting reports on whether Arc is a bona fide E3 ligase substrate [22]. The consensus guidelines for angelman syndrome (AS) consider abnormal sleep-wake cycles and diminished need for sleep as associated features [23]. The Global AS Registry is web-based and allows parents and guardians worldwide to register, provide informed consent, and enter data on individuals with AS [24]. Understanding the role of social information processing deficits in the emergence of psychotic disorders is a crucial challenge in the management of these patients [25].

To better understand how loss of maternal UBE3A function derails brain development, we analyzed brain Structure in a maternal Ube3a knock-out mouse model of AS [26]. Moreover, our study suggests that CMA is prone to misdiagnosis for imprinting disorders such as PWS/AS, though it is considered a highly useful tool for copy Number variations [27]. Recent studies have also suggested that lncRNAs are more abundant in the human brain and are involved in neurodevelopment and neurodevelopmental disorders, including autism spectrum disorders (ASDs) [28]. FISH assay using D15Z4 probes indicated that the SMC was a pseudodicentric chromosome derived from chromosome 15 [29].

References: 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ,

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