Clinical impact and in vitro characterization of ADNP variants in pediatric patients / Chuanhui GE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 5p. Titre : Clinical impact and in vitro characterization of ADNP variants in pediatric patients Type de document : texte imprimé Auteurs : Chuanhui GE, Auteur ; Yuxin TIAN, Auteur ; Chunchun HU, Auteur ; Lianni MEI, Auteur ; Dongyun LI, Auteur ; Ping DONG, Auteur ; Ying ZHANG, Auteur ; Huiping LI, Auteur ; Daijing SUN, Auteur ; Wenzhu PENG, Auteur ; Xiu XU, Auteur ; Yan JIANG, Auteur ; Qiong XU, Auteur Article en page(s) : 5p. Langues : Anglais (eng) Mots-clés : Humans  Child  Intellectual Disability/genetics  Autism Spectrum Disorder/genetics  HEK293 Cells  Neuroblastoma  Transcription Factors  Nerve Tissue Proteins  Homeodomain Proteins/genetics  ADNP syndrome  ADNP variants  Autism spectrum disorder  Global developmental delay  Hvdas  Helsmoortel-Van der Aa syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS. En ligne : https://dx.doi.org/10.1186/s13229-024-00584-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Clinical impact and in vitro characterization of ADNP variants in pediatric patients [texte imprimé] / Chuanhui GE, Auteur ; Yuxin TIAN, Auteur ; Chunchun HU, Auteur ; Lianni MEI, Auteur ; Dongyun LI, Auteur ; Ping DONG, Auteur ; Ying ZHANG, Auteur ; Huiping LI, Auteur ; Daijing SUN, Auteur ; Wenzhu PENG, Auteur ; Xiu XU, Auteur ; Yan JIANG, Auteur ; Qiong XU, Auteur . - 5p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 5p. Mots-clés : Humans  Child  Intellectual Disability/genetics  Autism Spectrum Disorder/genetics  HEK293 Cells  Neuroblastoma  Transcription Factors  Nerve Tissue Proteins  Homeodomain Proteins/genetics  ADNP syndrome  ADNP variants  Autism spectrum disorder  Global developmental delay  Hvdas  Helsmoortel-Van der Aa syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS. En ligne : https://dx.doi.org/10.1186/s13229-024-00584-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Walking Alongside: Chinese Mothers’ Lived Experiences of Supporting Autistic Youth on the Journey to Employment / Ping DONG in Autism, 30-9 (September 2026)  

Public ISBD [article]  inAutism > 30-9 (September 2026) . - p.2350-2365 Titre : Walking Alongside: Chinese Mothers’ Lived Experiences of Supporting Autistic Youth on the Journey to Employment Type de document : texte imprimé Auteurs : Ping DONG, Auteur ; Tianxi XU, Auteur Article en page(s) : p.2350-2365 Langues : Anglais (eng) Mots-clés : autism  mother  transition  employment  qualitative research  China Index. décimale : PER Périodiques Résumé : Mothers’ persistent involvement is a critical but underexplored area of autistic youth’s transition to employment. Using a qualitative research design, this study interviewed five mothers, two fathers, five autistic youth, and seven teachers to explore the lived experiences of Chinese mothers who supported autistic youth towards employment. By foregrounding mothers’ voices, five interconnected themes were developed and represented in a spiralling model: (1) navigating educational pathways, (2) preparing for employment from childhood, (3) building a long-term support system, (4) balancing hope and uncertainty in lifelong planning, and (5) redefining motherhood over time. These findings highlight that maternal support for autistic youth evolves across the lifespan, revealing the dynamic strategies and roles mothers adopt to foster their children’s development and work preparation, unfolding progressively as children move towards adulthood. These insights underscore the need for coordinated, lifelong autism services and targeted parent training programmes that strengthen family-centred and gender-sensitive support.Lay Abstract Supporting a child with autism as they grow into adulthood and enter the workforce can be a long and challenging journey. Mothers usually play a key role in helping autistic youth prepare for work. Yet, we don’t know much about how mothers support autistic youth as they prepare for work. This study aims to explore the experiences of Chinese mothers who have supported autistic youth towards employment. Through interviews with five mothers, two fathers, five autistic youths, and seven teachers, the research identifies five key aspects of mothers’ support: (a) helping children access schooling and manage their learning, (b) preparing them for future jobs from an early age, (c) building long-term support networks for autistic youth, (d) balancing hope and worry about the future, and (e) adapting their multiple roles as mothers over time. The study shows that maternal support is not limited to a single stage of autistic youth’s lives but evolves continuously from childhood into early adulthood. These findings reveal the various strategies and roles that mothers adopt to help their children, while also highlighting the need for services and programmes that can better help families. Understanding mothers’ experiences can help schools, policymakers, and service providers design support that prepares autistic young people for work while also caring for their caregivers’ well-being. En ligne : https://dx.doi.org/10.1177/13623613261467798 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=592 [article] Walking Alongside: Chinese Mothers’ Lived Experiences of Supporting Autistic Youth on the Journey to Employment [texte imprimé] / Ping DONG, Auteur ; Tianxi XU, Auteur . - p.2350-2365. Langues : Anglais (eng) in Autism > 30-9 (September 2026) . - p.2350-2365 Mots-clés : autism  mother  transition  employment  qualitative research  China Index. décimale : PER Périodiques Résumé : Mothers’ persistent involvement is a critical but underexplored area of autistic youth’s transition to employment. Using a qualitative research design, this study interviewed five mothers, two fathers, five autistic youth, and seven teachers to explore the lived experiences of Chinese mothers who supported autistic youth towards employment. By foregrounding mothers’ voices, five interconnected themes were developed and represented in a spiralling model: (1) navigating educational pathways, (2) preparing for employment from childhood, (3) building a long-term support system, (4) balancing hope and uncertainty in lifelong planning, and (5) redefining motherhood over time. These findings highlight that maternal support for autistic youth evolves across the lifespan, revealing the dynamic strategies and roles mothers adopt to foster their children’s development and work preparation, unfolding progressively as children move towards adulthood. These insights underscore the need for coordinated, lifelong autism services and targeted parent training programmes that strengthen family-centred and gender-sensitive support.Lay Abstract Supporting a child with autism as they grow into adulthood and enter the workforce can be a long and challenging journey. Mothers usually play a key role in helping autistic youth prepare for work. Yet, we don’t know much about how mothers support autistic youth as they prepare for work. This study aims to explore the experiences of Chinese mothers who have supported autistic youth towards employment. Through interviews with five mothers, two fathers, five autistic youths, and seven teachers, the research identifies five key aspects of mothers’ support: (a) helping children access schooling and manage their learning, (b) preparing them for future jobs from an early age, (c) building long-term support networks for autistic youth, (d) balancing hope and worry about the future, and (e) adapting their multiple roles as mothers over time. The study shows that maternal support is not limited to a single stage of autistic youth’s lives but evolves continuously from childhood into early adulthood. These findings reveal the various strategies and roles that mothers adopt to help their children, while also highlighting the need for services and programmes that can better help families. Understanding mothers’ experiences can help schools, policymakers, and service providers design support that prepares autistic young people for work while also caring for their caregivers’ well-being. En ligne : https://dx.doi.org/10.1177/13623613261467798 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=592

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