3 recherche sur le mot-clé 'disproportionate megalencephaly'

Differential Altered Auditory Event-Related Potential Responses in Young Boys on the Autism Spectrum With and Without Disproportionate Megalencephaly / R. DE MEO-MONTEIL in Autism Research, 12-8 (August 2019)  

Public ISBD [article]  inAutism Research > 12-8 (August 2019) . - p.1236-1250 Titre : Differential Altered Auditory Event-Related Potential Responses in Young Boys on the Autism Spectrum With and Without Disproportionate Megalencephaly Type de document : Texte imprimé et/ou numérique Auteurs : R. DE MEO-MONTEIL, Auteur ; Christine W. NORDAHL, Auteur ; David G. AMARAL, Auteur ; Sally J ROGERS, Auteur ; S. K. HAROOTONIAN, Auteur ; J. MARTIN, Auteur ; S. M. RIVERA, Auteur ; C. D. SARON, Auteur Article en page(s) : p.1236-1250 Langues : Anglais (eng) Mots-clés : Eeg  auditory processing  autism spectrum disorder  disproportionate megalencephaly  toddlers Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD), characterized by impairments in social communication and repetitive behaviors, often includes altered responses to sensory inputs as part of its phenotype. The neurobiological basis for altered sensory processing is not well understood. The UC Davis Medical Investigation of Neurodevelopmental Disorders Institute Autism Phenome Project is a longitudinal, multidisciplinary study of young children with ASD and age-matched typically developing (TD) controls. Previous analyses of the magnetic resonance imaging data from this cohort have shown that approximately 15% of boys with ASD have disproportionate megalencephaly (DM) or brain size to height ratio, that is 1.5 standard deviations above the TD mean. Here, we investigated electrophysiological responses to auditory stimuli of increasing intensity (50-80 dB) in young toddlers (27-48 months old). Analyses included data from 36 age-matched boys, of which 24 were diagnosed with ASD (12 with and 12 without DM; ASD-DM and ASD-N) and 12 TD controls. We found that the two ASD subgroups differed in their electrophysiological response patterns to sounds of increasing intensity. At early latencies (55-115 ms), ASD-N does not show a loudness-dependent response like TD and ASD-DM, but tends to group intensities by soft vs. loud sounds, suggesting differences in sensory sensitivity in this group. At later latencies (145-195 ms), only the ASD-DM group shows significantly higher amplitudes for loud sounds. Because no similar effects were found in ASD-N and TD groups, this may be related to their altered neuroanatomy. These results contribute to the effort to delineate ASD subgroups and further characterize physiological responses associated with observable phenotypes. Autism Res 2019, 12: 1236-1250. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Approximately 15% of boys with ASD have much bigger brains when compared to individuals with typical development. By recording brain waves (electroencephalography) we compared how autistic children, with or without big brains, react to sounds compared to typically developing controls. We found that brain responses in the big-brained group are different from the two other groups, suggesting that they represent a specific autism subgroup. En ligne : http://dx.doi.org/10.1002/aur.2137 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405 [article] Differential Altered Auditory Event-Related Potential Responses in Young Boys on the Autism Spectrum With and Without Disproportionate Megalencephaly [Texte imprimé et/ou numérique] / R. DE MEO-MONTEIL, Auteur ; Christine W. NORDAHL, Auteur ; David G. AMARAL, Auteur ; Sally J ROGERS, Auteur ; S. K. HAROOTONIAN, Auteur ; J. MARTIN, Auteur ; S. M. RIVERA, Auteur ; C. D. SARON, Auteur . - p.1236-1250. Langues : Anglais (eng) in Autism Research > 12-8 (August 2019) . - p.1236-1250 Mots-clés : Eeg  auditory processing  autism spectrum disorder  disproportionate megalencephaly  toddlers Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD), characterized by impairments in social communication and repetitive behaviors, often includes altered responses to sensory inputs as part of its phenotype. The neurobiological basis for altered sensory processing is not well understood. The UC Davis Medical Investigation of Neurodevelopmental Disorders Institute Autism Phenome Project is a longitudinal, multidisciplinary study of young children with ASD and age-matched typically developing (TD) controls. Previous analyses of the magnetic resonance imaging data from this cohort have shown that approximately 15% of boys with ASD have disproportionate megalencephaly (DM) or brain size to height ratio, that is 1.5 standard deviations above the TD mean. Here, we investigated electrophysiological responses to auditory stimuli of increasing intensity (50-80 dB) in young toddlers (27-48 months old). Analyses included data from 36 age-matched boys, of which 24 were diagnosed with ASD (12 with and 12 without DM; ASD-DM and ASD-N) and 12 TD controls. We found that the two ASD subgroups differed in their electrophysiological response patterns to sounds of increasing intensity. At early latencies (55-115 ms), ASD-N does not show a loudness-dependent response like TD and ASD-DM, but tends to group intensities by soft vs. loud sounds, suggesting differences in sensory sensitivity in this group. At later latencies (145-195 ms), only the ASD-DM group shows significantly higher amplitudes for loud sounds. Because no similar effects were found in ASD-N and TD groups, this may be related to their altered neuroanatomy. These results contribute to the effort to delineate ASD subgroups and further characterize physiological responses associated with observable phenotypes. Autism Res 2019, 12: 1236-1250. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Approximately 15% of boys with ASD have much bigger brains when compared to individuals with typical development. By recording brain waves (electroencephalography) we compared how autistic children, with or without big brains, react to sounds compared to typically developing controls. We found that brain responses in the big-brained group are different from the two other groups, suggesting that they represent a specific autism subgroup. En ligne : http://dx.doi.org/10.1002/aur.2137 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405

m6A-mRNA Reader YTHDF2 Identified as a Potential Risk Gene in Autism With Disproportionate Megalencephaly / Nicholas K. HAGHANI ; Gabriana N. LA ; Natasha Ann F. MARIANO ; José M. URIBE-SALAZAR ; Gulhan KAYA ; Melissa REGESTER ; Derek Sayre ANDREWS ; Christine Wu NORDAHL ; David G. AMARAL ; Megan Y. DENNIS in Autism Research, 18-5 (May 2025)  

Public ISBD [article]  inAutism Research > 18-5 (May 2025) . - p.966-982 Titre : m6A-mRNA Reader YTHDF2 Identified as a Potential Risk Gene in Autism With Disproportionate Megalencephaly Type de document : Texte imprimé et/ou numérique Auteurs : Nicholas K. HAGHANI, Auteur ; Gabriana N. LA, Auteur ; Natasha Ann F. MARIANO, Auteur ; José M. URIBE-SALAZAR, Auteur ; Gulhan KAYA, Auteur ; Melissa REGESTER, Auteur ; Derek Sayre ANDREWS, Auteur ; Christine Wu NORDAHL, Auteur ; David G. AMARAL, Auteur ; Megan Y. DENNIS, Auteur Article en page(s) : p.966-982 Langues : Anglais (eng) Mots-clés : autism  disproportionate megalencephaly  genetics  m6A-RNA modification  YTHDF2  zebrafish Index. décimale : PER Périodiques Résumé : ABSTRACT Among autistic individuals, a subphenotype of disproportionate megalencephaly (ASD-DM) seen at three years of age is associated with co-occurring intellectual disability and poorer prognoses later in life. However, many of the genes contributing to ASD-DM have yet to be delineated. In this study, we identified additional ASD-DM candidate genes with the aim to better define the genetic etiology of this subphenotype of autism. We expanded the previously studied sample size of ASD-DM individuals ten fold by including probands from the Autism Phenome Project and Simons Simplex Collection, totaling 766 autistic individuals meeting the criteria for megalencephaly or macrocephaly and revealing 154 candidate ASD-DM genes harboring de novo protein-impacting variants. Our findings include 14 high confidence autism genes and seven genes previously associated with DM. Five impacted genes have previously been associated with both autism and DM, including CHD8 and PTEN. By performing functional network analysis, we expanded to additional candidate genes, including one previously implicated in ASD-DM (PIK3CA) as well as 184 additional genes connected with ASD or DM alone. Using zebrafish, we modeled a de novo tandem duplication impacting YTHDF2, encoding an N6-methyladenosine (m6A)-mRNA reader, in an ASD-DM proband. Testing zebrafish CRISPR knockdown led to reduced head/brain size, while overexpressing YTHDF2 resulted in increased head/brain size matching that of the proband. Single-cell transcriptomes of YTHDF2 gain-of-function larvae point to reduced expression of Fragile-X-syndrome-associated FMRP-target genes globally and in the developing brain, providing insight into the mechanism underlying autistic phenotypes. We additionally discovered a variant impacting a different gene encoding an m6A reader, YTHDC1, in our ASD-DM cohort. Though we highlight only two cases to date, our study provides support for the m6A-RNA modification pathway as potentially contributing to this severe form of autism. En ligne : https://doi.org/10.1002/aur.3314 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=558 [article] m6A-mRNA Reader YTHDF2 Identified as a Potential Risk Gene in Autism With Disproportionate Megalencephaly [Texte imprimé et/ou numérique] / Nicholas K. HAGHANI, Auteur ; Gabriana N. LA, Auteur ; Natasha Ann F. MARIANO, Auteur ; José M. URIBE-SALAZAR, Auteur ; Gulhan KAYA, Auteur ; Melissa REGESTER, Auteur ; Derek Sayre ANDREWS, Auteur ; Christine Wu NORDAHL, Auteur ; David G. AMARAL, Auteur ; Megan Y. DENNIS, Auteur . - p.966-982. Langues : Anglais (eng) in Autism Research > 18-5 (May 2025) . - p.966-982 Mots-clés : autism  disproportionate megalencephaly  genetics  m6A-RNA modification  YTHDF2  zebrafish Index. décimale : PER Périodiques Résumé : ABSTRACT Among autistic individuals, a subphenotype of disproportionate megalencephaly (ASD-DM) seen at three years of age is associated with co-occurring intellectual disability and poorer prognoses later in life. However, many of the genes contributing to ASD-DM have yet to be delineated. In this study, we identified additional ASD-DM candidate genes with the aim to better define the genetic etiology of this subphenotype of autism. We expanded the previously studied sample size of ASD-DM individuals ten fold by including probands from the Autism Phenome Project and Simons Simplex Collection, totaling 766 autistic individuals meeting the criteria for megalencephaly or macrocephaly and revealing 154 candidate ASD-DM genes harboring de novo protein-impacting variants. Our findings include 14 high confidence autism genes and seven genes previously associated with DM. Five impacted genes have previously been associated with both autism and DM, including CHD8 and PTEN. By performing functional network analysis, we expanded to additional candidate genes, including one previously implicated in ASD-DM (PIK3CA) as well as 184 additional genes connected with ASD or DM alone. Using zebrafish, we modeled a de novo tandem duplication impacting YTHDF2, encoding an N6-methyladenosine (m6A)-mRNA reader, in an ASD-DM proband. Testing zebrafish CRISPR knockdown led to reduced head/brain size, while overexpressing YTHDF2 resulted in increased head/brain size matching that of the proband. Single-cell transcriptomes of YTHDF2 gain-of-function larvae point to reduced expression of Fragile-X-syndrome-associated FMRP-target genes globally and in the developing brain, providing insight into the mechanism underlying autistic phenotypes. We additionally discovered a variant impacting a different gene encoding an m6A reader, YTHDC1, in our ASD-DM cohort. Though we highlight only two cases to date, our study provides support for the m6A-RNA modification pathway as potentially contributing to this severe form of autism. En ligne : https://doi.org/10.1002/aur.3314 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=558

Persistence of megalencephaly in a subgroup of young boys with autism spectrum disorder / Lauren E. LIBERO in Autism Research, 9-11 (November 2016)  

Public ISBD [article]  inAutism Research > 9-11 (November 2016) . - p.1169-1182 Titre : Persistence of megalencephaly in a subgroup of young boys with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Lauren E. LIBERO, Auteur ; Christine W. NORDAHL, Auteur ; Deana D. LI, Auteur ; Emilio FERRER, Auteur ; Sally J ROGERS, Auteur ; David G. AMARAL, Auteur Article en page(s) : p.1169-1182 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  MRI  longitudinal  brain development  disproportionate megalencephaly Index. décimale : PER Périodiques Résumé : A recurring finding in autism spectrum disorder research is that head and brain growth is disproportionate to body growth in early childhood. Nordahl et al. (2011) demonstrated that this occurs in approximately 15% of boys with autism. While the literature suggests that brain growth normalizes at older ages, this has never been evaluated in a longitudinal study. The current study evaluated head circumference and total cerebral volume in 129 male children with autism and 49 age-matched, typically developing controls. We determined whether 3-year-old boys with brain size disproportionate to height (which we call disproportionate megalencephaly) demonstrated an abnormal trajectory of head growth from birth and whether they maintained an enlarged brain at 5 years of age. Findings were based on longitudinal, structural MRI data collected around 3, 4, and 5 years of age and head circumference data from medical records. At 3 years of age, 19 boys with autism had enlarged brains while 110 had brain sizes in the normal range. Boys with disproportionate megalencephaly had greater total cerebral, gray matter, and white matter volumes from 3–5 years compared to boys with autism and normal sized brains and typically developing boys, but no differences in body size. While head circumference did not differ between groups at birth, it was significantly greater in the disproportionate megalencephaly group by around 2 years. These data suggest that there is a subgroup of boys with autism who have brains disproportionate to body size and that this continues until at least 5 years of age. En ligne : http://dx.doi.org/10.1002/aur.1643 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=297 [article] Persistence of megalencephaly in a subgroup of young boys with autism spectrum disorder [Texte imprimé et/ou numérique] / Lauren E. LIBERO, Auteur ; Christine W. NORDAHL, Auteur ; Deana D. LI, Auteur ; Emilio FERRER, Auteur ; Sally J ROGERS, Auteur ; David G. AMARAL, Auteur . - p.1169-1182. Langues : Anglais (eng) in Autism Research > 9-11 (November 2016) . - p.1169-1182 Mots-clés : autism spectrum disorder  MRI  longitudinal  brain development  disproportionate megalencephaly Index. décimale : PER Périodiques Résumé : A recurring finding in autism spectrum disorder research is that head and brain growth is disproportionate to body growth in early childhood. Nordahl et al. (2011) demonstrated that this occurs in approximately 15% of boys with autism. While the literature suggests that brain growth normalizes at older ages, this has never been evaluated in a longitudinal study. The current study evaluated head circumference and total cerebral volume in 129 male children with autism and 49 age-matched, typically developing controls. We determined whether 3-year-old boys with brain size disproportionate to height (which we call disproportionate megalencephaly) demonstrated an abnormal trajectory of head growth from birth and whether they maintained an enlarged brain at 5 years of age. Findings were based on longitudinal, structural MRI data collected around 3, 4, and 5 years of age and head circumference data from medical records. At 3 years of age, 19 boys with autism had enlarged brains while 110 had brain sizes in the normal range. Boys with disproportionate megalencephaly had greater total cerebral, gray matter, and white matter volumes from 3–5 years compared to boys with autism and normal sized brains and typically developing boys, but no differences in body size. While head circumference did not differ between groups at birth, it was significantly greater in the disproportionate megalencephaly group by around 2 years. These data suggest that there is a subgroup of boys with autism who have brains disproportionate to body size and that this continues until at least 5 years of age. En ligne : http://dx.doi.org/10.1002/aur.1643 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=297