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From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study

Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show norm...

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Autores principales: Aghakhanyan, Gayane, Bonanni, Paolo, Randazzo, Giovanna, Nappi, Sara, Tessarotto, Federica, De Martin, Lara, Frijia, Francesca, De Marchi, Daniele, De Masi, Francesco, Kuppers, Beate, Lombardo, Francesco, Caramella, Davide, Montanaro, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023118/
https://www.ncbi.nlm.nih.gov/pubmed/27626634
http://dx.doi.org/10.1371/journal.pone.0162817
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author Aghakhanyan, Gayane
Bonanni, Paolo
Randazzo, Giovanna
Nappi, Sara
Tessarotto, Federica
De Martin, Lara
Frijia, Francesca
De Marchi, Daniele
De Masi, Francesco
Kuppers, Beate
Lombardo, Francesco
Caramella, Davide
Montanaro, Domenico
author_facet Aghakhanyan, Gayane
Bonanni, Paolo
Randazzo, Giovanna
Nappi, Sara
Tessarotto, Federica
De Martin, Lara
Frijia, Francesca
De Marchi, Daniele
De Masi, Francesco
Kuppers, Beate
Lombardo, Francesco
Caramella, Davide
Montanaro, Domenico
author_sort Aghakhanyan, Gayane
collection PubMed
description Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.
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spelling pubmed-50231182016-09-27 From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study Aghakhanyan, Gayane Bonanni, Paolo Randazzo, Giovanna Nappi, Sara Tessarotto, Federica De Martin, Lara Frijia, Francesca De Marchi, Daniele De Masi, Francesco Kuppers, Beate Lombardo, Francesco Caramella, Davide Montanaro, Domenico PLoS One Research Article Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS. Public Library of Science 2016-09-14 /pmc/articles/PMC5023118/ /pubmed/27626634 http://dx.doi.org/10.1371/journal.pone.0162817 Text en © 2016 Aghakhanyan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Aghakhanyan, Gayane
Bonanni, Paolo
Randazzo, Giovanna
Nappi, Sara
Tessarotto, Federica
De Martin, Lara
Frijia, Francesca
De Marchi, Daniele
De Masi, Francesco
Kuppers, Beate
Lombardo, Francesco
Caramella, Davide
Montanaro, Domenico
From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study
title From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study
title_full From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study
title_fullStr From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study
title_full_unstemmed From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study
title_short From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study
title_sort from cortical and subcortical grey matter abnormalities to neurobehavioral phenotype of angelman syndrome: a voxel-based morphometry study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023118/
https://www.ncbi.nlm.nih.gov/pubmed/27626634
http://dx.doi.org/10.1371/journal.pone.0162817
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