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UNC Study Could Lead To A Treatment For Angelman Syndrome
Results of a new study from the University of North Carolina at Chapel Hill may help pave the way to a treatment for a neurogenetic disorder often misdiagnosed as cerebral palsy or autism. Known as Angelman syndrome, or AS, its most characteristic feature is the absence or near absence of speech throughout the person's life. Occurring in one in 15,000 live births, other AS characteristics include intellectual and developmental delay, severe intellectual disability, seizures, sleep disturbance, motor and balance disorders... (Source: Health News from Medical News Today)

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Transcription Is Required to Establish Maternal Imprinting at the Prader-Willi Syndrome and Angelman Syndrome Locus
by Emily Y. Smith, Christopher R. Futtner, Stormy J. Chamberlain, Karen A. Johnstone, James L. Resnick The Prader-Willi syndrome (PWS [MIM 17620]) and Angelman syndrome (AS [MIM 105830]) locus is controlled by a bipartite imprinting center (IC) consisting of the PWS-IC and the AS-IC. The most widely accepted model of IC function proposes that the PWS-IC activates gene expression from the paternal allele, while the AS-IC acts to epigenetically inactivate the PWS-IC on the maternal allele, thus silencing the paternally expressed genes. Gene order and imprinting patterns at the PWS/AS locus are well conserved from human to mouse; however, a murine AS-IC has yet to be identified. We investigated a potential regulatory role for transcription from the Snrpn alternative upstream exons in sil...

[News & Analysis] Neurodevelopmental Disorders: New Hope for a Devastating Neurological Disorder
Scientists have identified a drug that, in mice, fixes the genetic defect behind Angelman syndrome, which robs victims of speech and leaves them with intellectual disabilities, movement and balance problems.Author: Greg Miller (Source: Science: Current Issue)

Angelman syndrome: Drugs to awaken a paternal gene
Nature advance online publication 21 December 2011. doi:10.1038/nature10784 Author: Arthur L. Beaudet Mutations in the maternal copy of the UBE3A gene cause a neurodevelopmental disorder known as Angelman syndrome. Drugs that activate the normally silenced paternal copy of this gene may be of therapeutic value. (Source: Nature AOP)

Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons
Authors: Hsien-Sung Huang, John A. Allen, Angela M. Mabb, Ian F. King, Jayalakshmi Miriyala, Bonnie Taylor-Blake, Noah Sciaky, J. Walter Dutton, Hyeong-Min Lee, Xin Chen, Jian Jin, Arlene S. Bridges, Mark J. Zylka, Bryan L. Roth & Benjamin D. Philpot Angelman syndrome is a severe neurodevelopmental disorder caused by deletion or mutation of the maternal allele of the ubiquitin protein ligase E3A (UBE3A). In neurons, the paternal allele of UBE3A is intact but epigenetically silenced, raising the possibility that Angelman syndrome could be treated by activating this silenced allele to restore functional UBE3A protein. Using an unbiased, high-content screen in primary cortical neurons from mice, we identify twelve topoisomerase I inhibitors and four topoisomerase II inhibitors that unsile...

Angelman syndrome: Drugs to awaken a paternal gene
Authors: Arthur L. Beaudet Mutations in the maternal copy of the UBE3A gene cause a neurodevelopmental disorder known as Angelman syndrome. Drugs that activate the normally silenced paternal copy of this gene may be of therapeutic value. See Letter p.185 (Source: Nature)

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Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons
Authors: Hsien-Sung Huang, John A. Allen, Angela M. Mabb, Ian F. King, Jayalakshmi Miriyala, Bonnie Taylor-Blake, Noah Sciaky, J. Walter Dutton, Hyeong-Min Lee, Xin Chen, Jian Jin, Arlene S. Bridges, Mark J. Zylka, Bryan L. Roth & Benjamin D. Philpot Angelman syndrome is a severe neurodevelopmental disorder caused by deletion or mutation of the maternal allele of the ubiquitin protein ligase E3A (UBE3A). In neurons, the paternal allele of UBE3A is intact but epigenetically silenced, raising the possibility that Angelman syndrome could be treated by activating this silenced allele to restore functional UBE3A protein. Using an unbiased, high-content screen in primary cortical neurons from mice, we identify twelve topoisomerase I inhibitors and four topoisomerase II inhibitors that u...

Epilepsy in four genetically determined syndromes of intellectual disability
Conclusions  The annotation highlights research describing disturbances in excitatory and inhibitory neurotransmitter systems, neuronal ion channel and glial functions that provide possible explanations for the co‐occurrence of seizures within several ID syndromes, in some cases suggesting possible avenues for research into novel therapeutic targets. Phenotypic overlaps between syndromes may also relate to roles for the implicated genes in different disturbances in linked biochemical pathways. (Source: Journal of Intellectual Disability Research)

X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction
Mutations in solute carrier family 9 isoform 6 on chromosome Xq26.3 encoding sodium–hydrogen exchanger 6, a protein mainly expressed in early and recycling endosomes are known to cause a complex and slowly progressive degenerative human neurological disease. Three resulting phenotypes have so far been reported: an X-linked Angelman syndrome-like condition, Christianson syndrome and corticobasal degeneration with tau deposition, with each characterized by severe intellectual disability, epilepsy, autistic behaviour and ataxia. Hypothesizing that a sodium–hydrogen exchanger 6 deficiency would most likely disrupt the endosomal–lysosomal system of neurons, we examined Slc9a6 knockout mice with tissue staining and related techniques commonly used to study lysosomal storage dis...

Intragenic deletion of UBE3A gene in 2 sisters with Angelman syndrome detected by MLPA
(Source: American Journal of Medical Genetics Part A)