25 recherche sur le mot-clé 'Mutation'

Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach / Sadhna RAO in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 12 p. Titre : Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach Type de document : texte imprimé Auteurs : Sadhna RAO, Auteur ; Anastasiia SADYBEKOV, Auteur ; David C. DEWITT, Auteur ; Joanna LIPKA, Auteur ; Vsevolod KATRITCH, Auteur ; Bruce E. HERRING, Auteur Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Humans  Autism Spectrum Disorder/genetics/metabolism  HEK293 Cells  Intellectual Disability/genetics/metabolism  Mutation  Mutation, Missense  Neurons/metabolism  Autism spectrum disorders  Glutamatergic neurotransmission  Missense mutations  Mutation modeling  Synaptic dysfunction  TRIO-related disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Glutamatergic synapse dysfunction is believed to underlie the development of Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) in many individuals. However, identification of genetic markers that contribute to synaptic dysfunction in these individuals is notoriously difficult. Based on genomic analysis, structural modeling, and functional data, we recently established the involvement of the TRIO-RAC1 pathway in ASD and ID. Furthermore, we identified a pathological de novo missense mutation hotspot in TRIO's GEF1 domain. ASD/ID-related missense mutations within this domain compromise glutamatergic synapse function and likely contribute to the development of ASD/ID. The number of ASD/ID cases with mutations identified within TRIO's GEF1 domain is increasing. However, tools for accurately predicting whether such mutations are detrimental to protein function are lacking. METHODS: Here we deployed advanced protein structural modeling techniques to predict potential de novo pathogenic and benign mutations within TRIO's GEF1 domain. Mutant TRIO-9 constructs were generated and expressed in CA1 pyramidal neurons of organotypic cultured hippocampal slices. AMPA receptor-mediated postsynaptic currents were examined in these neurons using dual whole-cell patch clamp electrophysiology. We also validated these findings using orthogonal co-immunoprecipitation and fluorescence lifetime imaging (FLIM-FRET) experiments to assay TRIO mutant overexpression effects on TRIO-RAC1 binding and on RAC1 activity in HEK293/T cells. RESULTS: Missense mutations in TRIO's GEF1 domain that were predicted to disrupt TRIO-RAC1 binding or stability were tested experimentally and found to greatly impair TRIO-9's influence on glutamatergic synapse function. In contrast, missense mutations in TRIO's GEF1 domain that were predicted to have minimal effect on TRIO-RAC1 binding or stability did not impair TRIO-9's influence on glutamatergic synapse function in our experimental assays. In orthogonal assays, we find most of the mutations predicted to disrupt binding display loss of function but mutants predicted to disrupt stability do not reflect our results from neuronal electrophysiological data. LIMITATIONS: We present a method to predict missense mutations in TRIO's GEF1 domain that may compromise TRIO function and test for effects in a limited number of assays. Possible limitations arising from the model systems employed here can be addressed in future studies. Our method does not provide evidence for whether these mutations confer ASD/ID risk or the likelihood that such mutations will result in the development of ASD/ID. CONCLUSIONS: Here we show that a combination of structure-based computational predictions and experimental validation can be employed to reliably predict whether missense mutations in the human TRIO gene impede TRIO protein function and compromise TRIO's role in glutamatergic synapse regulation. With the growing accessibility of genome sequencing, the use of such tools in the accurate identification of pathological mutations will be instrumental in diagnostics of ASD/ID. En ligne : https://dx.doi.org/10.1186/s13229-024-00590-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach [texte imprimé] / Sadhna RAO, Auteur ; Anastasiia SADYBEKOV, Auteur ; David C. DEWITT, Auteur ; Joanna LIPKA, Auteur ; Vsevolod KATRITCH, Auteur ; Bruce E. HERRING, Auteur . - 12 p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 12 p. Mots-clés : Humans  Autism Spectrum Disorder/genetics/metabolism  HEK293 Cells  Intellectual Disability/genetics/metabolism  Mutation  Mutation, Missense  Neurons/metabolism  Autism spectrum disorders  Glutamatergic neurotransmission  Missense mutations  Mutation modeling  Synaptic dysfunction  TRIO-related disorders Index. décimale : PER Périodiques Résumé : BACKGROUND: Glutamatergic synapse dysfunction is believed to underlie the development of Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) in many individuals. However, identification of genetic markers that contribute to synaptic dysfunction in these individuals is notoriously difficult. Based on genomic analysis, structural modeling, and functional data, we recently established the involvement of the TRIO-RAC1 pathway in ASD and ID. Furthermore, we identified a pathological de novo missense mutation hotspot in TRIO's GEF1 domain. ASD/ID-related missense mutations within this domain compromise glutamatergic synapse function and likely contribute to the development of ASD/ID. The number of ASD/ID cases with mutations identified within TRIO's GEF1 domain is increasing. However, tools for accurately predicting whether such mutations are detrimental to protein function are lacking. METHODS: Here we deployed advanced protein structural modeling techniques to predict potential de novo pathogenic and benign mutations within TRIO's GEF1 domain. Mutant TRIO-9 constructs were generated and expressed in CA1 pyramidal neurons of organotypic cultured hippocampal slices. AMPA receptor-mediated postsynaptic currents were examined in these neurons using dual whole-cell patch clamp electrophysiology. We also validated these findings using orthogonal co-immunoprecipitation and fluorescence lifetime imaging (FLIM-FRET) experiments to assay TRIO mutant overexpression effects on TRIO-RAC1 binding and on RAC1 activity in HEK293/T cells. RESULTS: Missense mutations in TRIO's GEF1 domain that were predicted to disrupt TRIO-RAC1 binding or stability were tested experimentally and found to greatly impair TRIO-9's influence on glutamatergic synapse function. In contrast, missense mutations in TRIO's GEF1 domain that were predicted to have minimal effect on TRIO-RAC1 binding or stability did not impair TRIO-9's influence on glutamatergic synapse function in our experimental assays. In orthogonal assays, we find most of the mutations predicted to disrupt binding display loss of function but mutants predicted to disrupt stability do not reflect our results from neuronal electrophysiological data. LIMITATIONS: We present a method to predict missense mutations in TRIO's GEF1 domain that may compromise TRIO function and test for effects in a limited number of assays. Possible limitations arising from the model systems employed here can be addressed in future studies. Our method does not provide evidence for whether these mutations confer ASD/ID risk or the likelihood that such mutations will result in the development of ASD/ID. CONCLUSIONS: Here we show that a combination of structure-based computational predictions and experimental validation can be employed to reliably predict whether missense mutations in the human TRIO gene impede TRIO protein function and compromise TRIO's role in glutamatergic synapse regulation. With the growing accessibility of genome sequencing, the use of such tools in the accurate identification of pathological mutations will be instrumental in diagnostics of ASD/ID. En ligne : https://dx.doi.org/10.1186/s13229-024-00590-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Electroconvulsive Therapy for Catatonia with mTOR Mutation / Charles B. MORMANDO in Journal of Autism and Developmental Disorders, 51-10 (October 2021)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3782-3783 Titre : Electroconvulsive Therapy for Catatonia with mTOR Mutation Type de document : texte imprimé Auteurs : Charles B. MORMANDO, Auteur ; John C. GARMAN, Auteur ; Cezary MIKOLUK, Auteur ; A. FRANCIS, Auteur Article en page(s) : p.3782-3783 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder  Catatonia/therapy  Electroconvulsive Therapy  Humans  Male  Mutation  TOR Serine-Threonine Kinases  Young Adult Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1007/s10803-020-04815-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453 [article] Electroconvulsive Therapy for Catatonia with mTOR Mutation [texte imprimé] / Charles B. MORMANDO, Auteur ; John C. GARMAN, Auteur ; Cezary MIKOLUK, Auteur ; A. FRANCIS, Auteur . - p.3782-3783. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 51-10 (October 2021) . - p.3782-3783 Mots-clés : Autism Spectrum Disorder  Catatonia/therapy  Electroconvulsive Therapy  Humans  Male  Mutation  TOR Serine-Threonine Kinases  Young Adult Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1007/s10803-020-04815-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=453

Transcriptomic profiling of unmethylated full mutation carriers implicates TET3 in FMR1 CGG repeat expansion methylation dynamics in fragile X syndrome / Grace FARMILOE in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Transcriptomic profiling of unmethylated full mutation carriers implicates TET3 in FMR1 CGG repeat expansion methylation dynamics in fragile X syndrome Type de document : texte imprimé Auteurs : Grace FARMILOE, Auteur ; Veronika BEJCZY, Auteur ; Elisabetta TABOLACCI, Auteur ; Rob WILLEMSEN, Auteur ; Frank JACOBS, Auteur Langues : Anglais (eng) Mots-clés : Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics/metabolism  Humans  DNA Methylation/genetics  Trinucleotide Repeat Expansion/genetics  Male  Gene Expression Profiling  Fibroblasts/metabolism  Female  Heterozygote  Mutation  Promoter Regions, Genetic  Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the expansion of a CGG repeat in the 5'UTR of the FMR1 (fragile X messenger ribonucleoprotein 1) gene. Healthy individuals possess a repeat 30-55 CGG units in length. Once the CGG repeat exceeds 200 copies it triggers methylation at the locus. This methylation covers the FMR1 promoter region and silences expression of the gene and the production of FMRP (fragile X messenger ribonucleoprotein). The loss of FMRP is responsible for a number of pathologies including neurodevelopmental delay and autism spectrum disorder. Methylation of the expanded repeat in the FMR1 locus is the causal factor for FXS, however it is not known why the expanded repeat triggers this epigenetic change or how exactly DNA methylation is established. Intriguingly, genetic engineering of expanded CGG repeats of over 300 copies in the FMR1 locus in mice remains unmethylated. Also in humans, in very rare cases, individuals can have an FMR1 CGG expansion > 200 copies but the locus remains unmethylated. These unmethylated full mutation (UFM) individuals give us a rare opportunity to investigate the mechanism of FMR1 promoter methylation. METHODS: Fibroblasts were obtained from a healthy control, an FXS patient and two unmethylated full expansion carriers. RNA was extracted and comparative transcriptomic analysis was performed on all samples. Whole genome sequencing was carried out on DNA from the two UFM carriers and the results analysed to investigate DNA variants that could explain the observed differences in gene expression. RESULTS: Our analyses focused on genes involved in epigenetic modification. We show that Tet methylcytosine dioxygenase 3 (TET3), a gene involved in DNA methylation, is significantly downregulated in UFM carriers compared to healthy controls or FXS patient derived cells. Genomic analyses reveal a number of rare variants present in the TET3 locus in UFM carriers when compared to the reference genome. However, no clear modifying TET3 variants were identified. CONCLUSION: Our results suggest that TET3 is a candidate factor responsible for the lack of methylation of the expanded FMR1 locus. Further analyses are needed to further elucidate this relationship, however given its potential to directly interact with CGG repeats and its ambiguous role in 5-hydroxy-methylation of CG containing sequences, TET3 is a strong candidate for further exploration. En ligne : https://dx.doi.org/10.1186/s11689-025-09609-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Transcriptomic profiling of unmethylated full mutation carriers implicates TET3 in FMR1 CGG repeat expansion methylation dynamics in fragile X syndrome [texte imprimé] / Grace FARMILOE, Auteur ; Veronika BEJCZY, Auteur ; Elisabetta TABOLACCI, Auteur ; Rob WILLEMSEN, Auteur ; Frank JACOBS, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/genetics/metabolism  Humans  DNA Methylation/genetics  Trinucleotide Repeat Expansion/genetics  Male  Gene Expression Profiling  Fibroblasts/metabolism  Female  Heterozygote  Mutation  Promoter Regions, Genetic  Adult Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the expansion of a CGG repeat in the 5'UTR of the FMR1 (fragile X messenger ribonucleoprotein 1) gene. Healthy individuals possess a repeat 30-55 CGG units in length. Once the CGG repeat exceeds 200 copies it triggers methylation at the locus. This methylation covers the FMR1 promoter region and silences expression of the gene and the production of FMRP (fragile X messenger ribonucleoprotein). The loss of FMRP is responsible for a number of pathologies including neurodevelopmental delay and autism spectrum disorder. Methylation of the expanded repeat in the FMR1 locus is the causal factor for FXS, however it is not known why the expanded repeat triggers this epigenetic change or how exactly DNA methylation is established. Intriguingly, genetic engineering of expanded CGG repeats of over 300 copies in the FMR1 locus in mice remains unmethylated. Also in humans, in very rare cases, individuals can have an FMR1 CGG expansion > 200 copies but the locus remains unmethylated. These unmethylated full mutation (UFM) individuals give us a rare opportunity to investigate the mechanism of FMR1 promoter methylation. METHODS: Fibroblasts were obtained from a healthy control, an FXS patient and two unmethylated full expansion carriers. RNA was extracted and comparative transcriptomic analysis was performed on all samples. Whole genome sequencing was carried out on DNA from the two UFM carriers and the results analysed to investigate DNA variants that could explain the observed differences in gene expression. RESULTS: Our analyses focused on genes involved in epigenetic modification. We show that Tet methylcytosine dioxygenase 3 (TET3), a gene involved in DNA methylation, is significantly downregulated in UFM carriers compared to healthy controls or FXS patient derived cells. Genomic analyses reveal a number of rare variants present in the TET3 locus in UFM carriers when compared to the reference genome. However, no clear modifying TET3 variants were identified. CONCLUSION: Our results suggest that TET3 is a candidate factor responsible for the lack of methylation of the expanded FMR1 locus. Further analyses are needed to further elucidate this relationship, however given its potential to directly interact with CGG repeats and its ambiguous role in 5-hydroxy-methylation of CG containing sequences, TET3 is a strong candidate for further exploration. En ligne : https://dx.doi.org/10.1186/s11689-025-09609-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Variable phenotypic expression of a MECP2 mutation in a family / Kimberly AUGENSTEIN in Journal of Neurodevelopmental Disorders, 1-4 (December 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-4 (December 2009) . - p.313 Titre : Variable phenotypic expression of a MECP2 mutation in a family Type de document : texte imprimé Auteurs : Kimberly AUGENSTEIN, Auteur ; Jane B. LANE, Auteur ; Antony HORTON, Auteur ; Carolyn SCHANEN, Auteur ; Alan K. PERCY, Auteur Article en page(s) : p.313 Langues : Anglais (eng) Mots-clés : Dystonia  Mecp2  Male  Mutation  Phenotype-genotype  Rett syndrome  X chromosome inactivation Index. décimale : PER Périodiques Résumé : We report a three generation family in which five members, three females and two males, demonstrate a 44 bp deletion (1164-1207del44) in the MECP2 gene associated with Rett syndrome, leading to a truncation of the C-terminus of the protein. Two of the three females and both males do not meet RTT criteria whereas the youngest female has classic RTT. Both males demonstrated a clear pattern of progressive involvement including dystonia. The transmitting females do not demonstrate features of RTT as a result of unbalanced X chromosome inactivation (XCI) and were only identified as carriers following the evaluation of the affected males and the girl with classic RTT. As such, accurate assessment of the precise frequency of MECP2 mutations in carrier females with mild cognitive impairment or borderline cognitive function will be under-represented unless an affected offspring is recognized. Strategies for accurate diagnosis in such instances should be considered carefully. En ligne : http://dx.doi.org/10.1007/s11689-009-9034-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342 [article] Variable phenotypic expression of a MECP2 mutation in a family [texte imprimé] / Kimberly AUGENSTEIN, Auteur ; Jane B. LANE, Auteur ; Antony HORTON, Auteur ; Carolyn SCHANEN, Auteur ; Alan K. PERCY, Auteur . - p.313. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-4 (December 2009) . - p.313 Mots-clés : Dystonia  Mecp2  Male  Mutation  Phenotype-genotype  Rett syndrome  X chromosome inactivation Index. décimale : PER Périodiques Résumé : We report a three generation family in which five members, three females and two males, demonstrate a 44 bp deletion (1164-1207del44) in the MECP2 gene associated with Rett syndrome, leading to a truncation of the C-terminus of the protein. Two of the three females and both males do not meet RTT criteria whereas the youngest female has classic RTT. Both males demonstrated a clear pattern of progressive involvement including dystonia. The transmitting females do not demonstrate features of RTT as a result of unbalanced X chromosome inactivation (XCI) and were only identified as carriers following the evaluation of the affected males and the girl with classic RTT. As such, accurate assessment of the precise frequency of MECP2 mutations in carrier females with mild cognitive impairment or borderline cognitive function will be under-represented unless an affected offspring is recognized. Strategies for accurate diagnosis in such instances should be considered carefully. En ligne : http://dx.doi.org/10.1007/s11689-009-9034-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342

WDFY3 mutation alters laminar position and morphology of cortical neurons / Zachary A. SCHAAF in Molecular Autism, 13 (2022)  

Public ISBD [article]  inMolecular Autism > 13 (2022) . - 27 p. Titre : WDFY3 mutation alters laminar position and morphology of cortical neurons Type de document : texte imprimé Auteurs : Zachary A. SCHAAF, Auteur ; Lyvin TAT, Auteur ; Noemi CANNIZZARO, Auteur ; Ralph GREEN, Auteur ; Thomas RULICKE, Auteur ; Simon HIPPENMEYER, Auteur ; Konstantinos S. ZARBALIS, Auteur Article en page(s) : 27 p. Langues : Anglais (eng) Mots-clés : Adaptor Proteins, Signal Transducing/genetics  Animals  Autistic Disorder/genetics  Autophagy-Related Proteins/genetics  Cerebral Cortex/cytology  Humans  Mice  Mutation  Neurogenesis/genetics  Neurons/cytology  Cerebral cortex  Dendrites  Dendritic spines  Excitatory neurons  Neuronal migration  Wdfy3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology. METHODS: Here, in an effort to untangle the origins of NMDs in Wdfy3(lacZ) mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques. RESULTS: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. LIMITATIONS: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation. CONCLUSIONS: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life. En ligne : http://dx.doi.org/10.1186/s13229-022-00508-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 [article] WDFY3 mutation alters laminar position and morphology of cortical neurons [texte imprimé] / Zachary A. SCHAAF, Auteur ; Lyvin TAT, Auteur ; Noemi CANNIZZARO, Auteur ; Ralph GREEN, Auteur ; Thomas RULICKE, Auteur ; Simon HIPPENMEYER, Auteur ; Konstantinos S. ZARBALIS, Auteur . - 27 p. Langues : Anglais (eng) in Molecular Autism > 13 (2022) . - 27 p. Mots-clés : Adaptor Proteins, Signal Transducing/genetics  Animals  Autistic Disorder/genetics  Autophagy-Related Proteins/genetics  Cerebral Cortex/cytology  Humans  Mice  Mutation  Neurogenesis/genetics  Neurons/cytology  Cerebral cortex  Dendrites  Dendritic spines  Excitatory neurons  Neuronal migration  Wdfy3 Index. décimale : PER Périodiques Résumé : BACKGROUND: Proper cerebral cortical development depends on the tightly orchestrated migration of newly born neurons from the inner ventricular and subventricular zones to the outer cortical plate. Any disturbance in this process during prenatal stages may lead to neuronal migration disorders (NMDs), which can vary in extent from focal to global. Furthermore, NMDs show a substantial comorbidity with other neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous work demonstrated focal neuronal migration defects in mice carrying loss-of-function alleles of the recognized autism risk gene WDFY3. However, the cellular origins of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide critical insight into WDFY3-dependent disease pathology. METHODS: Here, in an effort to untangle the origins of NMDs in Wdfy3(lacZ) mice, we employed mosaic analysis with double markers (MADM). MADM technology enabled us to genetically distinctly track and phenotypically analyze mutant and wild-type cells concomitantly in vivo using immunofluorescent techniques. RESULTS: We revealed a cell autonomous requirement of WDFY3 for accurate laminar positioning of cortical projection neurons and elimination of mispositioned cells during early postnatal life. In addition, we identified significant deviations in dendritic arborization, as well as synaptic density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant neurons in Wdfy3-MADM reporter mice at postnatal stages. LIMITATIONS: While Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD pathology that remain inaccessible to investigation in humans, like most animal models, they do not a perfectly replicate all aspects of human ASD biology. The lack of human data makes it indeterminate whether morphological deviations described here apply to ASD patients or some of the other neurodevelopmental conditions associated with WDFY3 mutation. CONCLUSIONS: Our genetic approach revealed several cell autonomous requirements of WDFY3 in neuronal development that could underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions. The results are also consistent with findings in other ASD animal models and patients and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity in postnatal life. En ligne : http://dx.doi.org/10.1186/s13229-022-00508-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491

Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice / Stijn VAN DE SOMPELE ; Clemence LIGNEUL ; Camille CHATELAIN ; Christophe BARREA ; Jason P. LERCH ; Beatrice M. FILIPPI ; Serpil ALKAN ; Elfride DE BAERE ; Jamie JOHNSTON ; Steven J. CLAPCOTE in Molecular Autism, 16 (2025)  

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Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics / Katherine CUMMINGS in Journal of Neurodevelopmental Disorders, 14 (2022)  

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Déploiement de la e-santé pour un enrichissement des pratiques de soins et de formation des orthophonistes / Lisette CAZELLET in Rééducation Orthophonique, 264 (Décembre 2015)

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Dietary intake and growth deficits in Rett syndrome-A cross-section study / Lee-Chin WONG in Autism Research, 14-7 (July 2021)  

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Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia / Kanako ISHIZUKA in Journal of Neurodevelopmental Disorders, 12 (2020)  

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