Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome / Joel FROHLICH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 37 p. Titre : Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome Type de document : texte imprimé Auteurs : Joel FROHLICH, Auteur ; Lawrence T. REITER, Auteur ; Vidya SARAVANAPANDIAN, Auteur ; Charlotte DISTEFANO, Auteur ; Scott HUBERTY, Auteur ; Carly HYDE, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; Peyman GOLSHANI, Auteur ; Andrei IRIMIA, Auteur ; Richard W. OLSEN, Auteur ; Joerg F. HIPP, Auteur ; Shafali S. JESTE, Auteur Article en page(s) : 37 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-019-0280-6.]. En ligne : http://dx.doi.org/10.1186/s13229-019-0288-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome [texte imprimé] / Joel FROHLICH, Auteur ; Lawrence T. REITER, Auteur ; Vidya SARAVANAPANDIAN, Auteur ; Charlotte DISTEFANO, Auteur ; Scott HUBERTY, Auteur ; Carly HYDE, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; Peyman GOLSHANI, Auteur ; Andrei IRIMIA, Auteur ; Richard W. OLSEN, Auteur ; Joerg F. HIPP, Auteur ; Shafali S. JESTE, Auteur . - 37 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 37 p. Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-019-0280-6.]. En ligne : http://dx.doi.org/10.1186/s13229-019-0288-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1 / Noelle D. GERMAIN in Molecular Autism, (August 2014)  

Public ISBD [article]  inMolecular Autism > (August 2014) . - p.1-19 Titre : Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1 Type de document : texte imprimé Auteurs : Noelle D. GERMAIN, Auteur ; Pin-Fang CHEN, Auteur ; Alex M. PLOCIK, Auteur ; Heather GLATT-DEELEY, Auteur ; Judith BROWN, Auteur ; James J. FINK, Auteur ; Kaitlyn A. BOLDUC, Auteur ; Tiwanna M. ROBINSON, Auteur ; Eric S. LEVINE, Auteur ; Lawrence T. REITER, Auteur ; Brenton R. GRAVELEY, Auteur ; Marc LALANDE, Auteur ; Stormy J. CHAMBERLAIN, Auteur Article en page(s) : p.1-19 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Duplications of the chromosome 15q11-q13.1 region are associated with an estimated 1 to 3% of all autism cases, making this copy number variation (CNV) one of the most frequent chromosome abnormalities associated with autism spectrum disorder (ASD). Several genes located within the 15q11-q13.1 duplication region including ubiquitin protein ligase E3A (UBE3A), the gene disrupted in Angelman syndrome (AS), are involved in neural function and may play important roles in the neurobehavioral phenotypes associated with chromosome 15q11-q13.1 duplication (Dup15q) syndrome. En ligne : http://dx.doi.org/10.1186/2040-2392-5-44 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] Gene expression analysis of human induced pluripotent stem cell-derived neurons carrying copy number variants of chromosome 15q11-q13.1 [texte imprimé] / Noelle D. GERMAIN, Auteur ; Pin-Fang CHEN, Auteur ; Alex M. PLOCIK, Auteur ; Heather GLATT-DEELEY, Auteur ; Judith BROWN, Auteur ; James J. FINK, Auteur ; Kaitlyn A. BOLDUC, Auteur ; Tiwanna M. ROBINSON, Auteur ; Eric S. LEVINE, Auteur ; Lawrence T. REITER, Auteur ; Brenton R. GRAVELEY, Auteur ; Marc LALANDE, Auteur ; Stormy J. CHAMBERLAIN, Auteur . - p.1-19. Langues : Anglais (eng) in Molecular Autism > (August 2014) . - p.1-19 Index. décimale : PER Périodiques Résumé : Duplications of the chromosome 15q11-q13.1 region are associated with an estimated 1 to 3% of all autism cases, making this copy number variation (CNV) one of the most frequent chromosome abnormalities associated with autism spectrum disorder (ASD). Several genes located within the 15q11-q13.1 duplication region including ubiquitin protein ligase E3A (UBE3A), the gene disrupted in Angelman syndrome (AS), are involved in neural function and may play important roles in the neurobehavioral phenotypes associated with chromosome 15q11-q13.1 duplication (Dup15q) syndrome. En ligne : http://dx.doi.org/10.1186/2040-2392-5-44 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

Mechanisms underlying the EEG biomarker in Dup15q syndrome / Joel FROHLICH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 29 p. Titre : Mechanisms underlying the EEG biomarker in Dup15q syndrome Type de document : texte imprimé Auteurs : Joel FROHLICH, Auteur ; Lawrence T. REITER, Auteur ; Vidya SARAVANAPANDIAN, Auteur ; Charlotte DISTEFANO, Auteur ; Scott HUBERTY, Auteur ; Carly HYDE, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; Peyman GOLSHANI, Auteur ; Andrei IRIMIA, Auteur ; Richard W. OLSEN, Auteur ; Joerg F. HIPP, Auteur ; Shafali S. JESTE, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gaba  Gabra5  Gabrb3  Gabrg3  Neurodevelopmental disorders  UBE3A Index. décimale : PER Périodiques Résumé : Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods: To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results: Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions: Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome. En ligne : https://dx.doi.org/10.1186/s13229-019-0280-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Mechanisms underlying the EEG biomarker in Dup15q syndrome [texte imprimé] / Joel FROHLICH, Auteur ; Lawrence T. REITER, Auteur ; Vidya SARAVANAPANDIAN, Auteur ; Charlotte DISTEFANO, Auteur ; Scott HUBERTY, Auteur ; Carly HYDE, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Carrie E. BEARDEN, Auteur ; Peyman GOLSHANI, Auteur ; Andrei IRIMIA, Auteur ; Richard W. OLSEN, Auteur ; Joerg F. HIPP, Auteur ; Shafali S. JESTE, Auteur . - 29 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 29 p. Mots-clés : Autism  Biomarkers  Dup15q syndrome  Eeg  Gaba  Gabra5  Gabrb3  Gabrg3  Neurodevelopmental disorders  UBE3A Index. décimale : PER Périodiques Résumé : Background: Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods: To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results: Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions: Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome. En ligne : https://dx.doi.org/10.1186/s13229-019-0280-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects / Claudia MILAZZO in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 45 Titre : UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects Type de document : texte imprimé Auteurs : Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur ; Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur Article en page(s) : 45 Langues : Anglais (eng) Mots-clés : Animals  Angelman Syndrome/genetics/metabolism  Ubiquitin-Protein Ligases/genetics/metabolism  Genomic Imprinting  Disease Models, Animal  Mice  Proteome/metabolism  Behavior, Animal  Male  Female  Oligonucleotides, Antisense  Angelman syndrome  Antisense oligonucleotide  Behavior  Imprinting defects  Mouse model  Proteome  were conducted in accordance with the European Commission Council Directive  2010/63/EU (CCD license AVD101002016791 and AVD10100202216352). Consent for  publication: All authors have approved the final manuscript and consent for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a severe neurodevelopmental disorder with only symptomatic treatment currently available. The primary cause of AS is loss of functional UBE3A protein. This can be caused by deletions in the maternal 15q11-q13 region, maternal AS-imprinting center defects (mICD), paternal uniparental disomy of chromosome 15 (UPD) or mutations within the UBE3A gene. Current mouse models are Ube3a-centric and do not address expression changes of other genes in the 15q11-q13 locus on the pathophysiology of AS. This limits the ability to discern differences in therapeutic responses to current UBE3A-targeting strategies and hampers the identification of novel therapeutics/co-therapeutics. METHODS: Using a mouse line that harbors a maternally inherited mutation affecting the AS-PWS imprinting center ('mICD mice'), we studied the impact of the mICD or UPD AS subtype on behavior, seizure susceptibility and proteome. Additionally, by using mice overexpressing two copies of Ube3a or antisense oligonucleotide (ASO) targeting Ube3a-ATS, we analyzed the impact of bi-allelic Ube3a activation on behavior and proteome. RESULTS: mICD mice showed 80% reduction in UBE3A protein, bi-allelic expression of Ube3a-ATS and Mkrn3-Snord115 gene cluster, leading to robust AS behavioral deficits and proteome alterations similar to Ube3a(m-/p+) mice. Genetic UBE3A overexpression in mICD mice, mimicking therapeutic strategies that effectively activate the biallelic silenced Ube3a gene, resulted in a complete rescue of all behavioral phenotypes, seizure susceptibility and proteome alterations. Subsequently, treatment with an antisense oligonucleotide (ASO) to directly activate the biallelic silenced Ube3a gene in mICD mice also resulted in efficient reinstatement of UBE3A, 30% higher relative to WT, alongside a partial rescue of behavioral phenotypes. LIMITATIONS: Despite using a highly robust AS-specific behavioral battery, we did not investigate readouts such as neuronal activity and sleep, for which impairments in Ube3a(m-/p+) mice were described. CONCLUSIONS: Taken together, these findings demonstrate that the loss of UBE3A protein is the primary factor underlying AS phenotypes in this mICD/UPD mouse model of AS, while the biallelic expressed genes in this locus play either a marginal or yet unidentified role. These findings also corroborate UBE3A reinstatement as an attractive therapeutic strategy for AS individuals carrying an mICD or UPD mutation. En ligne : https://dx.doi.org/10.1186/s13229-025-00675-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569 [article] UBE3A reinstatement restores behaviorand proteome in an Angelman syndrome mouse model of imprinting defects [texte imprimé] / Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur ; Claudia MILAZZO, Auteur ; Ramanathan NARAYANAN, Auteur ; Solveig BADILLO, Auteur ; Silvia WANG, Auteur ; Rosaisela ALMAND, Auteur ; Roos MONSHOUWER, Auteur ; Manuel TZOUROS, Auteur ; Sabrina GOLLING, Auteur ; Edwin J. MIENTJES, Auteur ; Stormy J. CHAMBERLAIN, Auteur ; Thomas KREMER, Auteur ; Ype ELGERSMA, Auteur . - 45. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 45 Mots-clés : Animals  Angelman Syndrome/genetics/metabolism  Ubiquitin-Protein Ligases/genetics/metabolism  Genomic Imprinting  Disease Models, Animal  Mice  Proteome/metabolism  Behavior, Animal  Male  Female  Oligonucleotides, Antisense  Angelman syndrome  Antisense oligonucleotide  Behavior  Imprinting defects  Mouse model  Proteome  were conducted in accordance with the European Commission Council Directive  2010/63/EU (CCD license AVD101002016791 and AVD10100202216352). Consent for  publication: All authors have approved the final manuscript and consent for  publication. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman Syndrome (AS) is a severe neurodevelopmental disorder with only symptomatic treatment currently available. The primary cause of AS is loss of functional UBE3A protein. This can be caused by deletions in the maternal 15q11-q13 region, maternal AS-imprinting center defects (mICD), paternal uniparental disomy of chromosome 15 (UPD) or mutations within the UBE3A gene. Current mouse models are Ube3a-centric and do not address expression changes of other genes in the 15q11-q13 locus on the pathophysiology of AS. This limits the ability to discern differences in therapeutic responses to current UBE3A-targeting strategies and hampers the identification of novel therapeutics/co-therapeutics. METHODS: Using a mouse line that harbors a maternally inherited mutation affecting the AS-PWS imprinting center ('mICD mice'), we studied the impact of the mICD or UPD AS subtype on behavior, seizure susceptibility and proteome. Additionally, by using mice overexpressing two copies of Ube3a or antisense oligonucleotide (ASO) targeting Ube3a-ATS, we analyzed the impact of bi-allelic Ube3a activation on behavior and proteome. RESULTS: mICD mice showed 80% reduction in UBE3A protein, bi-allelic expression of Ube3a-ATS and Mkrn3-Snord115 gene cluster, leading to robust AS behavioral deficits and proteome alterations similar to Ube3a(m-/p+) mice. Genetic UBE3A overexpression in mICD mice, mimicking therapeutic strategies that effectively activate the biallelic silenced Ube3a gene, resulted in a complete rescue of all behavioral phenotypes, seizure susceptibility and proteome alterations. Subsequently, treatment with an antisense oligonucleotide (ASO) to directly activate the biallelic silenced Ube3a gene in mICD mice also resulted in efficient reinstatement of UBE3A, 30% higher relative to WT, alongside a partial rescue of behavioral phenotypes. LIMITATIONS: Despite using a highly robust AS-specific behavioral battery, we did not investigate readouts such as neuronal activity and sleep, for which impairments in Ube3a(m-/p+) mice were described. CONCLUSIONS: Taken together, these findings demonstrate that the loss of UBE3A protein is the primary factor underlying AS phenotypes in this mICD/UPD mouse model of AS, while the biallelic expressed genes in this locus play either a marginal or yet unidentified role. These findings also corroborate UBE3A reinstatement as an attractive therapeutic strategy for AS individuals carrying an mICD or UPD mutation. En ligne : https://dx.doi.org/10.1186/s13229-025-00675-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569

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