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

Improving the early screening procedure for autism spectrum disorder in young children: Experience from a community-based model in shanghai / Chunyang LI in Autism Research, 11-9 (September 2018)  

Public ISBD [article]  inAutism Research > 11-9 (September 2018) . - p.1206-1217 Titre : Improving the early screening procedure for autism spectrum disorder in young children: Experience from a community-based model in shanghai Type de document : texte imprimé Auteurs : Chunyang LI, Auteur ; Guowei ZHU, Auteur ; Jingjing FENG, Auteur ; Qiong XU, Auteur ; Zhigang ZHOU, Auteur ; Bingrui ZHOU, Auteur ; Chunchun HU, Auteur ; Chaoyu LIU, Auteur ; Huiping LI, Auteur ; Yao WANG, Auteur ; Weili YAN, Auteur ; Xiaohu GE, Auteur ; Xiu XU, Auteur Année de publication : 2018 Article en page(s) : p.1206-1217 Langues : Anglais (eng) Mots-clés : Chat-23  China  autism spectrum disorder  community-based  early screening Index. décimale : PER Périodiques Résumé : Most children with autism spectrum disorder (ASD) are not diagnosed until the age of 4, thus missing the opportunity for early intervention. The objective of this study was to investigate the feasibility of an early screening program for ASD applied during well-child visits in a community-based sample. The study lasted for 4 years and was divided into two stages. Stage I involved the implementation of the basic screening model in 2014. Toddlers received level 1 screening via section A of the Chinese-validated version of the Checklist for Autism in Toddlers (CHAT-23) during 18- and 24-month well-child visits in Xuhui District, Shanghai, China. Screen-positive children were referred to receive section B of the CHAT-23 for level 2 screening, and those still screen-positive were referred to undergo diagnosis and evaluation. Stage II involved the implementation of the improved screening model from 2015 to 2017 with the following modifications: (a) an added observational component in level 1 screening; (b) telephone follow-ups with the screen-positive families; and (c) dissemination of information on ASD to families. The results showed that 42 of 22,247 screened children were diagnosed with ASD. The ASD diagnosis rates were 0.1% in Stage I and 0.21% in Stage II. The screen-positive rate and the show rate of referral for level 1 screening increased by 76.92% and 58.43%, respectively, in Stage II compared to Stage I. Our results suggest that with appropriate logistic support, this two-level screening model is feasible and effective for the early screening of ASD during well-child visits. Autism Res 2018, 11: 1206-1217. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Difficulty in the timely identification of autism spectrum disorder (ASD) results in missed opportunities for many ASD children to receive early intervention. In this study, we established an early screening model for ASD among children aged 18-24 months in the community by relying on the three-level child healthcare system in China. The results showed that this model can effectively identify and diagnose ASD in children at an early age and thus enable early intervention. En ligne : http://dx.doi.org/10.1002/aur.1984 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=369 [article] Improving the early screening procedure for autism spectrum disorder in young children: Experience from a community-based model in shanghai [texte imprimé] / Chunyang LI, Auteur ; Guowei ZHU, Auteur ; Jingjing FENG, Auteur ; Qiong XU, Auteur ; Zhigang ZHOU, Auteur ; Bingrui ZHOU, Auteur ; Chunchun HU, Auteur ; Chaoyu LIU, Auteur ; Huiping LI, Auteur ; Yao WANG, Auteur ; Weili YAN, Auteur ; Xiaohu GE, Auteur ; Xiu XU, Auteur . - 2018 . - p.1206-1217. Langues : Anglais (eng) in Autism Research > 11-9 (September 2018) . - p.1206-1217 Mots-clés : Chat-23  China  autism spectrum disorder  community-based  early screening Index. décimale : PER Périodiques Résumé : Most children with autism spectrum disorder (ASD) are not diagnosed until the age of 4, thus missing the opportunity for early intervention. The objective of this study was to investigate the feasibility of an early screening program for ASD applied during well-child visits in a community-based sample. The study lasted for 4 years and was divided into two stages. Stage I involved the implementation of the basic screening model in 2014. Toddlers received level 1 screening via section A of the Chinese-validated version of the Checklist for Autism in Toddlers (CHAT-23) during 18- and 24-month well-child visits in Xuhui District, Shanghai, China. Screen-positive children were referred to receive section B of the CHAT-23 for level 2 screening, and those still screen-positive were referred to undergo diagnosis and evaluation. Stage II involved the implementation of the improved screening model from 2015 to 2017 with the following modifications: (a) an added observational component in level 1 screening; (b) telephone follow-ups with the screen-positive families; and (c) dissemination of information on ASD to families. The results showed that 42 of 22,247 screened children were diagnosed with ASD. The ASD diagnosis rates were 0.1% in Stage I and 0.21% in Stage II. The screen-positive rate and the show rate of referral for level 1 screening increased by 76.92% and 58.43%, respectively, in Stage II compared to Stage I. Our results suggest that with appropriate logistic support, this two-level screening model is feasible and effective for the early screening of ASD during well-child visits. Autism Res 2018, 11: 1206-1217. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Difficulty in the timely identification of autism spectrum disorder (ASD) results in missed opportunities for many ASD children to receive early intervention. In this study, we established an early screening model for ASD among children aged 18-24 months in the community by relying on the three-level child healthcare system in China. The results showed that this model can effectively identify and diagnose ASD in children at an early age and thus enable early intervention. En ligne : http://dx.doi.org/10.1002/aur.1984 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=369

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