Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions of the gene UBE3A or deletion of chromosome 15 at 15q11-q13, which encompasses UBE3A and several other genes, including GABRB3, GABRA5, GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (β3, α5, γ3). Individuals with deletions are generally more impaired than those with other genotypes, but the underlying pathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesis that genes other than UBE3A located on 15q11-q13 cause differences in pathophysiology between AS genotypes.
METHODS: We compared spectral power of clinical EEG recordings from children (1-18 years of age) with a deletion genotype (n = 37) or a nondeletion genotype (n = 21) and typically developing children without Angelman syndrome (n = 48).
RESULTS: We found elevated theta power (peak frequency: 5.3 Hz) and diminished beta power (peak frequency: 23 Hz) in the deletion genotype compared with the nondeletion genotype as well as excess broadband EEG power (1-32 Hz) peaking in the delta frequency range (peak frequency: 2.8 Hz), shared by both genotypes but stronger for the deletion genotype at younger ages.
CONCLUSIONS: Our results provide strong evidence for the contribution of non-UBE3A neuronal pathophysiology in deletion AS and suggest that hemizygosity of the GABRB3-GABRA5-GABRG3 gene cluster causes abnormal theta and beta EEG oscillations that may underlie the more severe clinical phenotype. Our work improves the understanding of AS pathophysiology and has direct implications for the development of AS treatments and biomarkers.
| Errataetall: |
CommentIn: Biol Psychiatry. 2019 May 1;85(9):e45-e46. - PMID 30999987 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:85 |
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| Enthalten in: |
Biological psychiatry - 85(2019), 9 vom: 01. Mai, Seite 752-759 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Frohlich, Joel [VerfasserIn] |
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| Links: |
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| Themen: |
Angelman syndrome |
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| Anmerkungen: |
Date Completed 30.03.2020 Date Revised 02.05.2020 published: Print-Electronic ClinicalTrials.gov: NCT00296764 CommentIn: Biol Psychiatry. 2019 May 1;85(9):e45-e46. - PMID 30999987 Citation Status MEDLINE |
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| doi: |
10.1016/j.biopsych.2019.01.008 |
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| PPN (Katalog-ID): |
NLM294503625 |
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| 245 | 1 | 0 | |a Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes |
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| 500 | |a Date Completed 30.03.2020 | ||
| 500 | |a Date Revised 02.05.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT00296764 | ||
| 500 | |a CommentIn: Biol Psychiatry. 2019 May 1;85(9):e45-e46. - PMID 30999987 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by either disruptions of the gene UBE3A or deletion of chromosome 15 at 15q11-q13, which encompasses UBE3A and several other genes, including GABRB3, GABRA5, GABRG3, encoding gamma-aminobutyric acid type A receptor subunits (β3, α5, γ3). Individuals with deletions are generally more impaired than those with other genotypes, but the underlying pathophysiology remains largely unknown. Here, we used electroencephalography (EEG) to test the hypothesis that genes other than UBE3A located on 15q11-q13 cause differences in pathophysiology between AS genotypes | ||
| 520 | |a METHODS: We compared spectral power of clinical EEG recordings from children (1-18 years of age) with a deletion genotype (n = 37) or a nondeletion genotype (n = 21) and typically developing children without Angelman syndrome (n = 48) | ||
| 520 | |a RESULTS: We found elevated theta power (peak frequency: 5.3 Hz) and diminished beta power (peak frequency: 23 Hz) in the deletion genotype compared with the nondeletion genotype as well as excess broadband EEG power (1-32 Hz) peaking in the delta frequency range (peak frequency: 2.8 Hz), shared by both genotypes but stronger for the deletion genotype at younger ages | ||
| 520 | |a CONCLUSIONS: Our results provide strong evidence for the contribution of non-UBE3A neuronal pathophysiology in deletion AS and suggest that hemizygosity of the GABRB3-GABRA5-GABRG3 gene cluster causes abnormal theta and beta EEG oscillations that may underlie the more severe clinical phenotype. Our work improves the understanding of AS pathophysiology and has direct implications for the development of AS treatments and biomarkers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Angelman syndrome | |
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| 650 | 4 | |a GABRB3-GABRA5-GABRG3 gene cluster | |
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| 700 | 1 | |a Miller, Meghan T |e verfasserin |4 aut | |
| 700 | 1 | |a Bird, Lynne M |e verfasserin |4 aut | |
| 700 | 1 | |a Garces, Pilar |e verfasserin |4 aut | |
| 700 | 1 | |a Purtell, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Hoener, Marius C |e verfasserin |4 aut | |
| 700 | 1 | |a Philpot, Benjamin D |e verfasserin |4 aut | |
| 700 | 1 | |a Sidorov, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Wen-Hann |e verfasserin |4 aut | |
| 700 | 1 | |a Hernandez, Maria-Clemencia |e verfasserin |4 aut | |
| 700 | 1 | |a Rotenberg, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Jeste, Shafali S |e verfasserin |4 aut | |
| 700 | 1 | |a Krishnan, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Khwaja, Omar |e verfasserin |4 aut | |
| 700 | 1 | |a Hipp, Joerg F |e verfasserin |4 aut | |
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