|
Prader-Willi Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642-two selective inhibitors of euchromatic histone lysine N-methyltransferase-2 (EHMT2, also known as G9a)-activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116, in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m<sup>+</sup>/p<sup>ΔS-U</sup>).
|
28024084 |
2017 |
|
Prader-Willi Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
AS is a single gene disorder, caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, while PWS is still considered a contiguous gene disorder.
|
24363065 |
2014 |
|
Prader-Willi Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Interestingly, topoisomerase inhibitors, including topotecan, were recently identified in an unbiased drug screen for compounds that could reverse the silent paternal allele of Ube3a in neurons, but the mechanism of topotecan action on the PWS/AS locus is unknown.
|
23918391 |
2013 |
|
Prader-Willi Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Absence of paternally expressed genes in this region cause Prader-Willi syndrome (PWS), whereas absence of the maternally expressed UBE3A gene causes Angelman syndrome (AS).
|
22426236 |
2012 |
|
Prader-Willi Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The mice showed partial activation of paternal Ube3a, with decreased expression of Ube3a-ATS but not any imprinting defects in the Prader-Willi syndrome/Angelman syndrome region.
|
22493002 |
2012 |
|
Prader-Willi Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The panel comprises three Prader Willi syndrome materials (two with different paternal deletions, and one with maternal uniparental disomy (UPD)) and three Angelman syndrome materials (one with a maternal deletion, one with paternal UPD or an epigenetic imprinting centre defect, and one with a UBE3A point mutation).
|
21587322 |
2011 |
|
Prader-Willi Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
These iPSC models of genomic imprinting disorders will facilitate investigation of the AS and PWS disease processes and allow study of the developmental timing and mechanism of UBE3A repression in human neurons.
|
20876107 |
2010 |
|
Prader-Willi Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, AS patients with a deletion of the entire PWS/AS locus often have more severe traits than patients with point mutations in UBE3A suggesting that other genes contribute to the syndrome.
|
19894069 |
2010 |
|
Prader-Willi Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Lack of a functional paternal copy of 15q11-q13 causes PWS; lack of a functional maternal copy of UBE3A, a gene within 15q11-q13, causes AS.
|
18627066 |
2008 |
|
Prader-Willi Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Quantitative real-time RT-PCR analysis of PWS and AS samples with paternal and maternal 15q11-13 deletions revealed a paternal expression bias of GABRB3, while RTT brain samples showed a significant reduction in GABRB3 and UBE3A.
|
17339270 |
2007 |
|
Prader-Willi Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The existing mouse models of PWS that lack the expression of multiple genes, including Snrpn, Ube3a, and many intronic snoRNA genes, are characterized by 80%-100% neonatal lethality.
|
16075369 |
2005 |
|
Prader-Willi Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
However, two genes previously identified as maternally expressed (UBE3A and ATP10C) showed a significant increase in expression in UPD cell lines compared with control and PWS deletion subjects.
|
12920063 |
2003 |
|
Prader-Willi Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Our findings support the hypothesis that the functional loss of maternal UBE3A gene activity is sufficient to cause AS and that the deleted region does not contain genes or other structures that are involved in PWS.
|
12210318 |
2002 |
|
Prader-Willi Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Paternal deletion from Snrpn to Ube3a in the mouse causes hypotonia, growth retardation and partial lethality and provides evidence for a gene contributing to Prader-Willi syndrome.
|
10400982 |
1999 |