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

Effects of Parent-Implemented Early Start Denver Model Intervention on Chinese Toddlers with Autism Spectrum Disorder: A Non-Randomized Controlled Trial / Bingrui ZHOU in Autism Research, 11-4 (April 2018)  

Public ISBD [article]  inAutism Research > 11-4 (April 2018) . - p.654-666 Titre : Effects of Parent-Implemented Early Start Denver Model Intervention on Chinese Toddlers with Autism Spectrum Disorder: A Non-Randomized Controlled Trial Type de document : texte imprimé Auteurs : Bingrui ZHOU, Auteur ; Qiong XU, Auteur ; Huiping LI, Auteur ; Ying ZHANG, Auteur ; Yao WANG, Auteur ; Sally J. ROGERS, Auteur ; Xiu XU, Auteur Année de publication : 2018 Article en page(s) : p.654-666 Langues : Anglais (eng) Mots-clés : Parent-implemented Early Start Denver Model (P-ESDM)  autism spectrum disorder  early intervention  parenting stress  toddler Index. décimale : PER Périodiques Résumé : To evaluate the effects of a 26-week, high-intensity, parent-implemented Early Start Denver Model (P-ESDM) intervention on developmental outcomes, severity of autism spectrum disorder (ASD), and parental stress of ASD toddlers in China. Subjects in P-ESDM group (n = 23) were recruited from 1.5- to 2.5-year-old toddlers who were screened positive in Xuhui and Minhang Districts and were diagnosed with ASD. A community (comparison) group of age-matched toddlers with ASD (n = 20) was recruited from other areas. Subjects of the P-ESDM group attended 1.5-hr parent coaching per week for 26 weeks, and those in the community group received interventions available from communities. Assessments were conducted at baseline (T1) and 26 weeks later (T2). After adjusting for baseline differences between the two groups, P-ESDM group demonstrated greater improvement than the community group in general development, especially in Language domain. Neither group demonstrated significant change in ASD severity, but the P-ESDM group showed greater improvement in social affect, parent-reported social communication and symbolic play than community group did. Finally, parents in P-ESDM group experienced decreased parenting stress while those in community group showed an opposite trend, though the differences did not reach significant association with the P-ESDM intervention. Chinese toddlers with ASD receiving 26 weeks of P-ESDM via regular coaching sessions showed significant greater improvement than those receiving community interventions in multiple aspects of development including social communications. These findings add support to the importance of providing early screening, diagnosis, and immediate referral for evidence-based interventions to improve outcome of young children with ASD. Autism Res 2018, 11: 654-666. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The development of early screening and diagnosis of autism spectrum disorder (ASD) in China has highlighted the importance of early intervention for young children with ASD. Our current study demonstrated that parent-implemented Early Start Denver Model (P-ESDM) via coaching from professionals improved developmental outcomes, especially in the language domain, and social communicational behaviors of Chinese toddlers with ASD. P-ESDM may help parents in China provide effective early intervention to their children with ASD via improving their skills when they are still at a waiting list for services or lack access to intervention, and has the potential to alleviate their parenting stress. En ligne : http://dx.doi.org/10.1002/aur.1917 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=358 [article] Effects of Parent-Implemented Early Start Denver Model Intervention on Chinese Toddlers with Autism Spectrum Disorder: A Non-Randomized Controlled Trial [texte imprimé] / Bingrui ZHOU, Auteur ; Qiong XU, Auteur ; Huiping LI, Auteur ; Ying ZHANG, Auteur ; Yao WANG, Auteur ; Sally J. ROGERS, Auteur ; Xiu XU, Auteur . - 2018 . - p.654-666. Langues : Anglais (eng) in Autism Research > 11-4 (April 2018) . - p.654-666 Mots-clés : Parent-implemented Early Start Denver Model (P-ESDM)  autism spectrum disorder  early intervention  parenting stress  toddler Index. décimale : PER Périodiques Résumé : To evaluate the effects of a 26-week, high-intensity, parent-implemented Early Start Denver Model (P-ESDM) intervention on developmental outcomes, severity of autism spectrum disorder (ASD), and parental stress of ASD toddlers in China. Subjects in P-ESDM group (n = 23) were recruited from 1.5- to 2.5-year-old toddlers who were screened positive in Xuhui and Minhang Districts and were diagnosed with ASD. A community (comparison) group of age-matched toddlers with ASD (n = 20) was recruited from other areas. Subjects of the P-ESDM group attended 1.5-hr parent coaching per week for 26 weeks, and those in the community group received interventions available from communities. Assessments were conducted at baseline (T1) and 26 weeks later (T2). After adjusting for baseline differences between the two groups, P-ESDM group demonstrated greater improvement than the community group in general development, especially in Language domain. Neither group demonstrated significant change in ASD severity, but the P-ESDM group showed greater improvement in social affect, parent-reported social communication and symbolic play than community group did. Finally, parents in P-ESDM group experienced decreased parenting stress while those in community group showed an opposite trend, though the differences did not reach significant association with the P-ESDM intervention. Chinese toddlers with ASD receiving 26 weeks of P-ESDM via regular coaching sessions showed significant greater improvement than those receiving community interventions in multiple aspects of development including social communications. These findings add support to the importance of providing early screening, diagnosis, and immediate referral for evidence-based interventions to improve outcome of young children with ASD. Autism Res 2018, 11: 654-666. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The development of early screening and diagnosis of autism spectrum disorder (ASD) in China has highlighted the importance of early intervention for young children with ASD. Our current study demonstrated that parent-implemented Early Start Denver Model (P-ESDM) via coaching from professionals improved developmental outcomes, especially in the language domain, and social communicational behaviors of Chinese toddlers with ASD. P-ESDM may help parents in China provide effective early intervention to their children with ASD via improving their skills when they are still at a waiting list for services or lack access to intervention, and has the potential to alleviate their parenting stress. En ligne : http://dx.doi.org/10.1002/aur.1917 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=358

Refractive Status and Amblyopia Risk Factors in Chinese Children with Autism Spectrum Disorder / Jing WANG in Journal of Autism and Developmental Disorders, 48-5 (May 2018)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 48-5 (May 2018) . - p.1530-1536 Titre : Refractive Status and Amblyopia Risk Factors in Chinese Children with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Jing WANG, Auteur ; Gang DING, Auteur ; Ying LI, Auteur ; Ning HUA, Auteur ; Nan WEI, Auteur ; Xiaoli QI, Auteur ; Yuxian NING, Auteur ; Ying ZHANG, Auteur ; Xue LI, Auteur ; Jun LI, Auteur ; Linlin SONG, Auteur ; Xuehan QIAN, Auteur Année de publication : 2018 Article en page(s) : p.1530-1536 Langues : Anglais (eng) Mots-clés : Amblyopia  Autism  Children  Refractive status  Risk factor  Strabismus Index. décimale : PER Périodiques Résumé : Amblyopia risk factors in children with autism spectrum disorders (ASD) are usually hard to detect in early childhood due to poor cooperation and has not been reported in the Chinese population. We screened 168 Chinese children with ASD, aged between 3 and 8 years, and 264 age-matched neurotypical children with Spot photoscreener and basic ophthalmologic examinations. Children with ASD were found to have normal refractive status but significantly higher incidence of strabismus (16.1%), compared with control children (1.5%) (p < 0.01). Most of the cases of strabismus found in children with ASD were classified as esodeviation. Strabismus in children with ASD should be considered more seriously as an amblyopia risk factor by ophthalmologists and other healthcare professionals. En ligne : http://dx.doi.org/10.1007/s10803-017-3387-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=355 [article] Refractive Status and Amblyopia Risk Factors in Chinese Children with Autism Spectrum Disorder [texte imprimé] / Jing WANG, Auteur ; Gang DING, Auteur ; Ying LI, Auteur ; Ning HUA, Auteur ; Nan WEI, Auteur ; Xiaoli QI, Auteur ; Yuxian NING, Auteur ; Ying ZHANG, Auteur ; Xue LI, Auteur ; Jun LI, Auteur ; Linlin SONG, Auteur ; Xuehan QIAN, Auteur . - 2018 . - p.1530-1536. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 48-5 (May 2018) . - p.1530-1536 Mots-clés : Amblyopia  Autism  Children  Refractive status  Risk factor  Strabismus Index. décimale : PER Périodiques Résumé : Amblyopia risk factors in children with autism spectrum disorders (ASD) are usually hard to detect in early childhood due to poor cooperation and has not been reported in the Chinese population. We screened 168 Chinese children with ASD, aged between 3 and 8 years, and 264 age-matched neurotypical children with Spot photoscreener and basic ophthalmologic examinations. Children with ASD were found to have normal refractive status but significantly higher incidence of strabismus (16.1%), compared with control children (1.5%) (p < 0.01). Most of the cases of strabismus found in children with ASD were classified as esodeviation. Strabismus in children with ASD should be considered more seriously as an amblyopia risk factor by ophthalmologists and other healthcare professionals. En ligne : http://dx.doi.org/10.1007/s10803-017-3387-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=355

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