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Submicroscopic 11p13 deletion including the elongator acetyltransferase complex subunit 4 gene in a girl with language failure, intellectual disability and congenital malformations: A case report
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作者 Jaime Toral-Lopez Luz María González Huerta +1 位作者 Olga Messina-Baas Sergio A Cuevas-Covarrubias 《World Journal of Clinical Cases》 SCIE 2020年第21期5296-5303,共8页
BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,tr... BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,treatment is only rehabilitation and surgery for cleft lip and palate.CASE SUMMARY The proband was a 2-years-8-months-old girl.Familial history was negative for congenital malformations or intellectual disability.The patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and palate.Brain magnetic resonance imaging showed cortical atrophy and band heterotopia.Her motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were detected.CONCLUSION There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 deletion.We describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular defect.Additional clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3. 展开更多
关键词 Submicroscopic 11p13 deletion Elongator acetyltransferase complex subunit 4 gene Language failure intellectual disability Congenital malformations Case report
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Empirically supported psychological treatments:The challenges of comorbid psychiatric and behavioral disorders in people with intellectual disability
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作者 Laura E Gómez Patricia Navas +1 位作者 MiguelÁngel Verdugo Marc J Tassé 《World Journal of Psychiatry》 SCIE 2021年第11期1039-1052,共14页
This paper reviews the current state of knowledge on psychological interventions with empirical evidence of efficacy in treating common psychiatric and behavioral disorders in people with intellectual disability(ID)at... This paper reviews the current state of knowledge on psychological interventions with empirical evidence of efficacy in treating common psychiatric and behavioral disorders in people with intellectual disability(ID)at all stages of their life.We begin with a brief presentation of what is meant by psychiatric and behavioral disorders in this population,along with an explanation of some of the factors that contribute to the increased psychosocial vulnerability of this group to present with these problems.We then conduct a review of empirically supported psychological therapies used to treat psychiatric and behavioral disorders in people with ID.The review is structured around the three generations of therapies:Applied behavior analysis(e.g.,positive behavior support),cognitive behavioral therapies(e.g.,mindfulness-based cognitive therapy),and contextual therapies(e.g.,dialectical behavior therapy).We conclude with some recommendations for professional practice in the fields of ID and psychiatry. 展开更多
关键词 Behavior disorder intellectual disability PSYCHIATRY Applied behavior analysis Cognitive behavioral therapies Contextual therapies
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Students With Intellectual Disability Learn How to Write With Motivation and Joy
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作者 Ann-Katrin Swärd Anders Karlsson 《Psychology Research》 2020年第11期423-437,共15页
Reading and writing can be seen as two sides of the same coin but have different demands for the writer and the reader to handle.The aim of this article is to focus on writing,how to create texts when students have in... Reading and writing can be seen as two sides of the same coin but have different demands for the writer and the reader to handle.The aim of this article is to focus on writing,how to create texts when students have intellectual disabilities and how students with intellectual disabilities have improved their writing skills through an intervention study.Writing will be highlighted from different perspectives,mostly about how writing can be supported through a structural way of working.When it comes to reading and reading difficulties,many studies have been done from different aspects of these topics.Most of these studies are among students with typical intellectual development.Studies about writing development and difficulties are fewer in number than studies about reading,but these are also mostly about children with typical development.When it comes to students with intellectual disability,studies about reading are rare and even rarer when it comes to writing.With this article,we will shed light on how writing difficulties can occur in general development and also when students have intellectual disability.The intervention study presented in this article will give some examples of how teachers can support every student’s writing development. 展开更多
关键词 writing development writing difficulties intellectual disability INTERVENTION
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Neurobiology of Neuronal Network Alteration in Intellectual Disability Related to Fetal Alcohol Spectrum Disorders
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作者 Abdoulaye Bâ 《Journal of Behavioral and Brain Science》 2022年第3期43-81,共39页
The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations ... The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations on neuronal network components underlying information processing, for further understanding of intellectual disability related to FASD. Abnormal neurodevelopmental events related to alcohol-damaged fetal brain included neurogenesis inhibition, aberrant migration, impaired differentiation, exacerbated apoptosis, impaired axon outgrowth and branching altering synaptogenesis and synaptic plasticity, abnormal GABAergic interneurons triggering synaptic inhibitory/excitatory imbalance, reduced myelinogenesis causing injured white matter in prefrontal lobe and atrophied corpus callosum compromising interhemispheric information transfer, the whole compromising neuronal network scaffolding which may lead to biased information processing with deficits in executive function. What added to these abnormalities are smaller gray matter and reduced hippocampus, resulting in cognition and memory failures. As a whole, these developmental disorders may underlie intellectual disability related to FASD. In rodents, these neuronal network components matured mainly during the second and third trimesters equivalents of human gestation. Transferability of results from animal to human was also discussed. It was hoped that the understanding of alcohol-induced neuronal networks failure mechanisms during the developing brain may lay a foundation for prospective new treatments and interventions. 展开更多
关键词 Fetal Alcohol Spectrum Disorders intellectual disability Neuronal Network Axogenesis SYNAPTOGENESIS Myelinogenesis
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Strengthening Social Skills in Students With an Intellectual Disability in Secondary Education
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作者 Drossinou-Korea Maria Panopoulos Nikolaos 《Sino-US English Teaching》 2017年第6期345-359,共15页
During recent decades, one of education's most important issues is the idea of inclusion regarding the students' full participation to the mutual school environment. In addition, in the international scientific bibl... During recent decades, one of education's most important issues is the idea of inclusion regarding the students' full participation to the mutual school environment. In addition, in the international scientific bibliography, it is stated that children with Intellectual Disability (ID) can integrate socially at school. However, the social benefits of inclusive education cannot always be reached. Studies have shown that just putting students with ID in a common school is not always adequate, as their social abilities are insufficient and because of that interventions are required. In this paper, we will examine school inclusion of students with ID having in mind that it is connected firstly to the modification of educational techniques using a Targeted, Individual, Structured, Integrated Program for Students with Special Educational Needs (TISIPfSENs). We will focus to the enhancement of their social skills facing school as one of their educational areas inside the community. The results showed that educational interventions that are focused on the enforcement of social skills are a basic priority for the inclusion of students with ID inside the school community. 展开更多
关键词 intellectual disability social skills TISIPfSENs
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Prevalence of intellectual disability in India:A meta-analysis
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作者 Paul Swamidhas Sudhakar Russell Sahana Nagaraj +7 位作者 Ashvini Vengadavaradan Sushila Russell Priya Mary Mammen Satya Raj Shankar Shonima Aynipully Viswanathan Richa Earnest Swetha Madhuri Chikkala Grace Rebekah 《World Journal of Clinical Pediatrics》 2022年第2期206-214,共9页
BACKGROUND Burden due to intellectual disability(ID) is only third to the depressive disorders and anxiety disorders in India. This national burden significantly contributes to the global burden of ID and hence one ha... BACKGROUND Burden due to intellectual disability(ID) is only third to the depressive disorders and anxiety disorders in India. This national burden significantly contributes to the global burden of ID and hence one has to think globally and act locally to reduce this burden. At its best the collective prevalence of ID is in the form of narrative reviews. There is an urgent need to document the summary prevalence of ID to enhance further policymaking, national programs and resource allocation.AIM To establish the summary prevalence of ID during the past 60 years in India.METHODS Two researchers independently and electronically searched Pub Med, Scopus, and the Cochrane library from January 1961 to December 2020 using appropriate search terms. Two other investigators extracted the study design, setting, participant characteristics, and measures used to identify ID. Two other researchers appraised the quality of the studies using the Joanna Briggs Institute critical appraisal format for Prevalence Studies. Funnel plot and Egger’s regression test were used to ascertain the publication and small study effect on the prevalence. To evaluate the summary prevalence of ID, we used the random effects model with arcsine square-root transformation. Heterogeneity of I^(2)≥ 50% was considered substantial and we determined the heterogeneity with meta-regression. The analyses were performed using STATA(version 16).RESULTS Nineteen studies were included in the meta-analysis. There was publication bias;the trim-and-fill method was used to further ascertain bias. Concerns with control of confounders and the reliable measure of outcome were noted in the critical appraisal. The summary prevalence of ID was 2% [(95%CI: 2%, 3%);I^(2)= 98%] and the adjusted summary prevalence was 1.4%. Meta-regression demonstrated that age of the participants was statistically significantly related to the prevalence;other factors did not influence the prevalence or heterogeneity.CONCLUSION The summary prevalence of ID in India was established to be 2% taking into consideration the individual prevalence studies over the last six decades. This knowledge should improve the existing disability and mental health policies, national programs and service delivery to reduce the national and global burden associated with ID. 展开更多
关键词 INDIA intellectual disability PREVALENCE Children and adolescents META-ANALYSIS
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Cytogenetic Diagnosis and Analysis of the Clinical Profile of Individuals with Non-down Syndrome Intellectual Disability
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作者 Fantin, C. Prazeres, V. G. M. +3 位作者 Benzaquem, D. C. Fernandes, E. R. Q. G. S. Oliveira, D. p. Ribeiro-Lima, J. C. 《Journal of Pharmacy and Pharmacology》 2017年第11期812-820,共9页
Chromosomal alterations are the main causes of genetic diseases. One of the characteristics of certain genetic syndromes is ID (intellectual disability) presented by the individual in varying degrees. The study of t... Chromosomal alterations are the main causes of genetic diseases. One of the characteristics of certain genetic syndromes is ID (intellectual disability) presented by the individual in varying degrees. The study of the ID, its etiology, association or not with chromosomal abnormalities and a clinical diagnosis associated with the examination of karyotype are important aspects to consider when providing genetic counseling for families. Due to the lack of similar studies and of easy access to cytogenetic services for the Amazonian population, this study aimed to contribute to the advancement of this line of study in the state, analyzing the karyotype of individuals with ID, not Down Syndrome treated at the APAE-Manaus and identifying the main types of chromosomal alterations in the individuals analyzed. Analyzes were performed of the clinical diagnosis through investigation of the data from the interview and medical records as well as analysis of the karyotype of 31 patients with non-Down syndrome ID, attended in the APAE-Manaus. Of these subjects, 20 were female and 11 male. The results showed only 2 cases of chromosome abnormalities are detectable by classical cytogenetics, one of mosaic Turner syndrome and one a heterochromatic variant. It is therefore necessary to complement the study with the addition of molecular techniques for the investigation of microdeletions and/or other alterations not detectable through the banding technique, mainly for individuals whose dysmorphisms indicate a suspected syndrome. 展开更多
关键词 intellectual disability classical cytogenetics G banding.
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Associated Factors of Dental Caries among Intellectually Disabled Persons in Specialized Centers of Ouagadougou
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作者 Jocelyne Valerie Gare Filwende Dan Kientega +3 位作者 Ouedraogo Carole Nathaie Tenin Ouattara Seydou Kabore Wendpoulomde Aime Désire Nicolas Meda 《Open Journal of Epidemiology》 2024年第2期297-311,共15页
Introduction: Several studies have reported a high prevalence of dental caries among the people with intellectual disabilities. In order to identify the sociodemographic, clinical and behavioral factors associated wit... Introduction: Several studies have reported a high prevalence of dental caries among the people with intellectual disabilities. In order to identify the sociodemographic, clinical and behavioral factors associated with it, we conducted a study in specialized centers welcoming subjects with intellectual disabilities in Ouagadougou (Burkina Faso). Objectives: The objective of this study was to identify the factors associated with it among intellectually disabled in the specialized centers of Ouagadougou. Methods: The study was cross-sectional analytical. The survey took place between November 2020 and January 2021 among people with intellectual disabilities in reception centers receiving a grant from the Ministry of Women, National Solidarity, Family and Humanitarian Action. Data collection was done with a questionnaire adapted from the World Health Organization (WHO) and dental caries was recorded according to WHO criteria in decayed, missing or filled teeth generating a DMF index. Logistic regression was used to identify factors associated with the presence of dental caries. Results: A total of 193 participants were included in the study with an average age of 12.4 years ± 7.9. The overall prevalence of caries measured with the DMF index was 58.6% 95% CI [51.2 - 65.8]. It was significantly associated with female gender (OR = 4.2;95% CI [1.4 - 12.5], p = 0,01), the clinical form of mental illness (epilepsy OR = 3.8 95%;CI [1.2 - 12.7], p = 0,02, trisomy OR = 5.0;95% CI [1.1 - 22.9], p = 0,03, motor autonomy OR = 0.2 95%;CI [0.1 - 0.7], p = 0,01) and at use of toothpaste OR = 9.33;95% CI [1.05 - 82.7], p = 0,04. Conclusion: Dental caries remains a very present pathology in most people living with an intellectual disability. Also, it is necessary to put in place prevention strategies to reduce its prevalence and improve access to oral care for these people. 展开更多
关键词 Dental Caries Mental disability intellectual disability Associated Factors OUAGADOUGOU
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The Role of Music Therapy in Supporting Intellectually Disabled Youth in Senegal
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作者 Raymond Birane Youm Kadidiatou Diarra +1 位作者 Mathias Pouye Jean Augustin Diégane Tine 《Health》 2024年第5期521-534,共14页
Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual... Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID. 展开更多
关键词 Music Therapy YOUNG intellectual Disabilities Senegal
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Understanding Behavioral Manifestations of Obsessive-Compulsive Disorder in People with Intellectual Disabilities—A Qualitative Study
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作者 Lena Grüter Matthias Grünke 《Open Journal of Psychiatry》 2024年第2期67-90,共24页
Background: There is limited knowledge about obsessive-compulsive disorder (OCD) in people with intellectual disabilities (IDs). This paper describes the manifestation of compulsive behaviors associated with OCD at th... Background: There is limited knowledge about obsessive-compulsive disorder (OCD) in people with intellectual disabilities (IDs). This paper describes the manifestation of compulsive behaviors associated with OCD at the behavioral level in people with ID in institutionalized settings. The aim was to gain nuanced insight into appropriate understanding and classification in this specific context, and derive implications for research and practice. Methods: Individual cases of people with ID (n = 7) were studied to assess compulsive symptoms through two days of on-site observation of the person with ID within the institution, guided group discussions (n = 28), and semi-structured interviews with key informants and caregivers of the person with ID (n = 20). Caregiver ratings of the compulsive behavior checklist were compiled. Data were analyzed using qualitative content analysis. Results: All forms of OCD were present. Characteristics of compulsive behaviors in people with ID at the behavioral level included less complex and more obvious compulsive acts, immediate responses, signs of tension, motor restlessness, facial expression changes, repetition, need for predictability, time-consuming behaviors, and aggressive reactions when these acts were interrupted. Some of the compulsive behaviors corresponded to the ICD-11 OCD code 6B20, and others to compulsions as a psychological symptom (MB23.4). Conclusions: OCD may manifest atypically at the behavioral level in people with ID, posing significant challenges for accurate classification due to symptom ambiguity. Follow-up differential diagnostic studies are needed to more accurately identify and differentiate OCD symptoms in people with ID. Further, disorder-specific guidelines for recognizing OCD in people with ID are needed for institutionalized settings without psychiatric-psychotherapeutic expertise. 展开更多
关键词 People with intellectual Disabilities Obsessive-Compulsive Disorder Compulsive Behavior DIAGNOSTICS Differential Diagnosis
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Performance of the Autism Spectrum Rating Scale and Social Responsiveness Scale in Identifying Autism Spectrum Disorder Among Cases of Intellectual Disability 被引量:6
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作者 Chunpei Li Hao Zhou +5 位作者 Tianqi Wang Shasha Long Xiaonan Du Xiu Xu Weili Yan Yi Wang 《Neuroscience Bulletin》 SCIE CAS CSCD 2018年第6期972-980,共9页
The Autism Spectrum Rating Scale(ASRS) and the Social Responsiveness Scale(SRS) have been widely used for screening autism spectrum disorder(ASD) in the general population during epidemiological studies, but studies o... The Autism Spectrum Rating Scale(ASRS) and the Social Responsiveness Scale(SRS) have been widely used for screening autism spectrum disorder(ASD) in the general population during epidemiological studies, but studies of individuals with intellectual disability(ID) are quite limited. Therefore, we recruited the parents/caregivers of 204 ASD cases, 71 ID cases aged 6–18 years from special education schools, and 402 typically developing(TD) children in the same age span from a communitybased population to complete the ASRS and SRS. The results showed that the ID group scored significantly lower on total and subscale scores than the ASD group on both scales(P \ 0.05) but higher than TD children(P \ 0.05).Receiver operating characteristic analyses demonstrated a similar fair performance in discriminating ASD from ID with the ASRS(area under the curve(AUC) = 0.709,sensitivity = 77.0%, specificity = 52.1%, positive predictive value(PPV) = 82.2%) and the SRS(AUC = 0.742,sensitivity = 59.8%, specificity = 77.5%, PPV = 88.4%).The results showed that individuals with ID had clear autistic traits and discriminating ASD from ID cases was quite challenging, while assessment tools such as ASRS and SRS, help to some degree. 展开更多
关键词 Autism spectrum disorder intellectual disability Screening accuracy Autism Spectrum Rating Scale Social Responsiveness Scale
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The Use of Goal Attainment Scaling in the Acupuncture of Children with Intellectual Disability 被引量:1
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作者 Si-Jia Zhang Dong Lin +4 位作者 Li-Li Lin Shi-Yi Qi Meng Gong Shi-Bin Li Jie Zhang 《World Journal of Traditional Chinese Medicine》 CAS 2022年第4期522-529,共8页
Objective: The therapeutic effect of acupuncture is often evaluated based on the experience and judgment of acupuncturists and the subjective feelings of patients. Thus, we investigated the suitability of goal attainm... Objective: The therapeutic effect of acupuncture is often evaluated based on the experience and judgment of acupuncturists and the subjective feelings of patients. Thus, we investigated the suitability of goal attainment scaling(GAS), an objective outcome measurements, to evaluate the responsiveness of children with intellectual disability to acupuncture therapy. Methods: This is an assessor-blinded, single-group cohort study that included 17 children with intellectual disabilities. The therapeutic effect of acupuncture was assessed by the T scores of GAS at four time points during the 3-month treatment. The responsiveness of GAS to acupuncture therapy was measured using the standardized response mean(SRM). Results: Compared with control, the 4-, 8-, and 12-week scores improved significantly after treatment(P < 0.01, P≤0.001,P≤0.001), with significant differences between each month(P < 0.01, P≤0.001, P≤0.001). Furthermore, all periods assessed GAS(to measure the therapeutic effect of acupuncture) showed marked responsiveness(SRMs >0.8). Conclusion: GAS is responsive in evaluating individual changes in the acupuncture treatment of children with intellectual disabilities. It is a feasible tool to match both the needs of children with intellectual disabilities and the clinical characteristics of acupuncture. 展开更多
关键词 ACUPUNCTURE goal attainment scaling intellectual disability
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A Novel MYCN Variant Associated with Intellectual Disability Regulates Neuronal Development
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作者 Xiuya Yu Liyuan Hu +7 位作者 Xu Liu Guodong Zhan Mei Mei Huijun Wang Xiaohua Zhang Zilong Qiu Wenhao Zhou Lin Yang 《Neuroscience Bulletin》 SCIE CAS CSCD 2018年第5期854-858,共5页
The V-MYC avian myelocytomatosis viral-related onco- gene, a neuroblastoma-derived gene (MYCN, MIM: 164840) located on chromosome 2p24, was previously found to be associated with Feingold syndrome 1 (FGLDS1, MIM:... The V-MYC avian myelocytomatosis viral-related onco- gene, a neuroblastoma-derived gene (MYCN, MIM: 164840) located on chromosome 2p24, was previously found to be associated with Feingold syndrome 1 (FGLDS1, MIM: 164280) [1]. FGLDS1 is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disabilities. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients [2]. Despite the involvement of intellectual disability in FGLDS1, the molecular mechanisms of the MYCN gene in regulating brain development remain largely unclear.Some truncated mutations in the N terminus of the MYCN have been identified in FGLDS1 [1, 3]. 展开更多
关键词 HEK A Novel MYCN Variant Associated with intellectual disability Regulates Neuronal Development
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A Study of Radiation-Induced Instability for the Gene Locus Associated with Intellectual Disorders or Developmental Delays
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作者 Alan Chant Ahmad Chaudary Christina M. Kraemer-Chant 《Advances in Biological Chemistry》 2023年第4期128-142,共15页
Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiatio... Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53. 展开更多
关键词 Ionizing Radiation Multiplex Ligation-Dependent Probe Amplification (MLPA) intellectual disability (ID) Developmental Delay (DD) p53 Tumor Suppressor
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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders 被引量:3
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作者 Helen M.Knight Merve DemirbugenÖz Adriana PerezGrovas-Saltijeral 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第6期1256-1261,共6页
The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNA... The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies. 展开更多
关键词 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification
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Transcriptional regulation in the development and dysfunction of neocortical projection neurons 被引量:1
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作者 Ningxin Wang Rong Wan Ke Tang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第2期246-254,共9页
Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord... Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations. 展开更多
关键词 autism spectrum disorders COGNITION DIFFERENTIATION excitatory circuits intellectual disability NEOCORTEX neurodevelopmental disorders projection neuron specification transcriptional regulation
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Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory 被引量:1
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作者 Baicheng Zhao Hang Zhang +5 位作者 Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第5期1133-1141,共9页
Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,K... Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation. 展开更多
关键词 behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current MRNA-SEQ
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CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system
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作者 Lin Yin Yalan Xu +9 位作者 Jie Mu Yu Leng Lei Ma Yu Zheng Ruizhi Li Yin Wang Peifeng Li Hai Zhu Dong Wang Jing Li 《Neural Regeneration Research》 SCIE CAS 2025年第8期2420-2432,共13页
The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS... The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders. 展开更多
关键词 autism spectrum disorder CENTROSOME CNKSR2 intellectual disability INTERACTOME mass spectrometry MICROTUBULE neurodevelopmental disease protein complexes protein-protein interactions
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Family empowerment and associated factors in Japanese families raising a child with severe motor and intellectual disabilities 被引量:3
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作者 Rie Wakimizu Hiroshi Fujioka +1 位作者 Kaori Nishigaki Akemi Matsuzawa 《International Journal of Nursing Sciences》 2018年第4期370-376,共7页
Objectives:Family caregivers raising children with severe motor and intellectual disabilities(SMID)experience the enormous burden of care.The concept of family empowerment is one of the important assessment indexes of... Objectives:Family caregivers raising children with severe motor and intellectual disabilities(SMID)experience the enormous burden of care.The concept of family empowerment is one of the important assessment indexes of family nursing from the perspective of providing comprehensive support for these families.The objective of this study was to identify the factors associated with the empowerment of families raising a child with SMID in Japan.Methods:We conducted a nationwide questionnaire survey involving 1659 primary caregivers raising a child with SMID through 89 special schools.We assessed the main outcomes using the Family Empowerment Scale(FES).We then conducted a multiple linear regression analysis to reveal the factors associated with family empowerment.Results:In total,1362 primary caregivers were included in our study.Our results show that factors contributing to high FES scores are higher age of the primary caregiver,higher education,greater recognition of regional support,lower childcare burden,higher utilization of home visit services,higher usage of a childcare institution,higher household income,and stronger family bonding.Conclusion:Healthcare professionals should carefully assess the state of family empowerment of the primary caregivers who are younger and those who have low education,low household income,high childcare burden,and fragile bonding with the family.Second,they should encourage such families to use regional support resources for childcare.That is,policy makers should consider ways to promote home visits and institutional services for the care of children with SMID,aiming especially for the provision of well-coordinated care and services. 展开更多
关键词 CAREGIVERS Child care Disabled children Family empowerment Home nursing intellectual disability Japan Social supports
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Utilizing the China Health and Retirement Longitudinal Study (CHARLS) to Understand the Aging of People Living in the Community with Intellectual and Developmental Disabilities
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作者 Philip McCallion Junrong Shi +1 位作者 Lisa A. Ferretti Mary McCarron 《Health》 2021年第1期47-59,共13页
There remain challenges in understanding the aging lives of people with intellectual and developmental disabilities. Method: A cross-sectional comparison of people with and without I/DD was created using China Health ... There remain challenges in understanding the aging lives of people with intellectual and developmental disabilities. Method: A cross-sectional comparison of people with and without I/DD was created using China Health and Retirement Longitudinal Study (CHARLS). A definition of I/DD was established, three samples were created: those with an assigned/described intellectual and developmental disability prior to age 22 years;those with similar impairments at and after age 22 years;and those in the population without an assigned/described impairment. Findings: Those with I/DD appeared to have greater health needs on initial analysis. People with an impairment similar to I/DD but occurring after age 22 years had the same or greater needs in subsequent analyses. Both groups had greater needs than those with no identified disability. Discussion: There must be greater efforts to discover those with I/DD who are already in existing datasets, greater attention to the full range of lives led by people with I/DD and inclusion of data from a broader range of countries. 展开更多
关键词 intellectual disability Developmental disability AGING China
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