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Intellectual Disability and Potassium Channelopathies: A Systematic Review.

ABSTRACT: Intellectual disability (ID) manifests prior to adulthood as severe limitations to intellectual function and adaptive behavior. The role of potassium channelopathies in ID is poorly understood. Therefore, we aimed to evaluate the relationship between ID and potassium channelopathies. We hypothesized that potassium channelopathies are strongly associated with ID initiation, and that both gain- and loss-of-function mutations lead to ID. This systematic review explores the burden of potassium channelopathies, possible mechanisms, advancements using animal models, therapies, and existing gaps. The literature search encompassed both PubMed and Embase up to October 2019. A total of 75 articles describing 338 cases were included in this review. Nineteen channelopathies were identified, affecting the following genes: KCNMA1, KCNN3, KCNT1, KCNT2, KCNJ10, KCNJ6, KCNJ11, KCNA2, KCNA4, KCND3, KCNH1, KCNQ2, KCNAB1, KCNQ3, KCNQ5, KCNC1, KCNB1, KCNC3, and KCTD3. Twelve of these genes presented both gain- and loss-of-function properties, three displayed gain-of-function only, three exhibited loss-of-function only, and one had unknown function. How gain- and loss-of-function mutations can both lead to ID remains largely unknown. We identified only a few animal studies that focused on the mechanisms of ID in relation to potassium channelopathies and some of the few available therapeutic options (channel openers or blockers) appear to offer limited efficacy. In conclusion, potassium channelopathies contribute to the initiation of ID in several instances and this review provides a comprehensive overview of which molecular players are involved in some of the most prominent disease phenotypes.

SUBMITTER: Kessi M

PROVIDER: S-EPMC7324798 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Intellectual Disability and Potassium Channelopathies: A Systematic Review.

Kessi Miriam M Chen Baiyu B Peng Jing J Tang Yulin Y Olatoutou Eleonore E He Fang F Yang Lifen L Yin Fei F

Frontiers in genetics 20200623

Intellectual disability (ID) manifests prior to adulthood as severe limitations to intellectual function and adaptive behavior. The role of potassium channelopathies in ID is poorly understood. Therefore, we aimed to evaluate the relationship between ID and potassium channelopathies. We hypothesized that potassium channelopathies are strongly associated with ID initiation, and that both gain- and loss-of-function mutations lead to ID. This systematic review explores the burden of potassium chann ...[more]

PMID: 32655623

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Project description:BackgroundCalcium ions are involved in several human cellular processes including corticogenesis, transcription, and synaptogenesis. Nevertheless, the relationship between calcium channelopathies (CCs) and intellectual disability (ID)/global developmental delay (GDD) has been poorly investigated. We hypothesised that CCs play a major role in the development of ID/GDD and that both gain- and loss-of-function variants of calcium channel genes can induce ID/GDD. As a result, we performed a systematic review to investigate the contribution of CCs, potential mechanisms underlying their involvement in ID/GDD, advancements in cell and animal models, treatments, brain anomalies in patients with CCs, and the existing gaps in the knowledge. We performed a systematic search in PubMed, Embase, ClinVar, OMIM, ClinGen, Gene Reviews, DECIPHER and LOVD databases to search for articles/records published before March 2021. The following search strategies were employed: ID and calcium channel, mental retardation and calcium channel, GDD and calcium channel, developmental delay and calcium channel.Main bodyA total of 59 reports describing 159 cases were found in PubMed, Embase, ClinVar, and LOVD databases. Variations in ten calcium channel genes including CACNA1A, CACNA1C, CACNA1I, CACNA1H, CACNA1D, CACNA2D1, CACNA2D2, CACNA1E, CACNA1F, and CACNA1G were found to be associated with ID/GDD. Most variants exhibited gain-of-function effect. Severe to profound ID/GDD was observed more for the cases with gain-of-function variants as compared to those with loss-of-function. CACNA1E, CACNA1G, CACNA1F, CACNA2D2 and CACNA1A associated with more severe phenotype. Furthermore, 157 copy number variations (CNVs) spanning calcium genes were identified in DECIPHER database. The leading genes included CACNA1C, CACNA1A, and CACNA1E. Overall, the underlying mechanisms included gain- and/ or loss-of-function, alteration in kinetics (activation, inactivation) and dominant-negative effects of truncated forms of alpha1 subunits. Forty of the identified cases featured cerebellar atrophy. We identified only a few cell and animal studies that focused on the mechanisms of ID/GDD in relation to CCs. There is a scarcity of studies on treatment options for ID/GDD both in vivo and in vitro.ConclusionOur results suggest that CCs play a major role in ID/GDD. While both gain- and loss-of-function variants are associated with ID/GDD, the mechanisms underlying their involvement need further scrutiny.

Project description:BackgroundDuring the COVID-19 pandemic, the vulnerabilities of certain groups of people have been highlighted, such as people with intellectual disability (ID). Although related research on ID has developed rapidly during the COVID-19 pandemic, the quantitative analysis of those research results has not been systematically performed through bibliometric analysis. Bibliometric analysis is a useful and rigorous method to explore large volumes of research data, and it allows researchers to extract quantitative information on distribution by author, time, country, and journal.AimThe aim of the present study is to comprehensively analyze the current status and developing trends in publications on ID research related to and conducted during the COVID-19 pandemic.MethodsA bibliometric analysis was performed using the Web of Science database. Biblioshiny software was used to analyze and visualize the following information: main information of dataset, annual scientific production, journals which published the most relevant sources, most-cited authors, most-cited countries, most-cited global documents, word-cloud of keywords authors have used, and both the co-occurrence and co-citation networks.ResultsA total of 450 publications were included. The average number of citations per document was 5.104. Among the top three journals, Journal of Applied Research in Intellectual Disabilities published 32 articles, Journal of Intellectual Disability Research published 29 articles, and British Journal of Learning Disabilities published 17 articles. The article with the title COVID-19 and People with Intellectual Disability: Impact of a Pandemic was the most cited with total 144 citations The United Kingdom had the most publications and had strong cooperative relationships with the United States, Canada, and Australia. The most popular keywords included mental health, autism, developmental disability, and lockdown. Thematic map analysis identified several possible clusters, including telemedicine, physical activities, and mental health.ConclusionThe present study provides a better understanding in this research field and may help clinicians, researchers and stakeholders to obtain more comprehensive view of ID and COVID-19. The insights gained from this analysis could inform future research.

Project description:INTRODUCTION:The aim of this review is to answer the following question: Does assistive technology contribute to social inclusion for people with intellectual disability? Previous research on assistive technology has focused on socioeconomic impacts such as education, employment and access to healthcare by people with intellectual disability. There is a need to consolidate evidence on the interaction between intellectual disability, assistive technology, community living and social inclusion. METHODS AND ANALYSIS:The review will consider studies from all settings: geographical, socioeconomic and care (institutional and community care), published in English. Studies reported in other languages with abstracts in English will be included if they can be translated using Google Translate, otherwise such studies will be included in the appendix. The review will include both qualitative and quantitative studies. The intervention in this review refers to the use of assistive technology to promote community participation or interpersonal relationships (social inclusion) for people with intellectual disability. The outcomes will be behavioural and social benefits of using assistive technology by people with intellectual disability. Enhanced interpersonal relationships and community participation by people with intellectual disability. Data analysis will be in two phases. The first phase will involve analysis of individual study designs separately. The second phase will be narrative/thematic synthesis of all study groups. ETHICS:The review will not create any ethical or safety concerns. DISSEMINATION:At least one peer-reviewed article in a leading journal such as the BMJ is planned. The findings will also be disseminated through a seminar session involving internal audience at Trinity College Dublin and within the Assistive Technologies for people with Intellectual Disability and Autism research programme. PROSPERO REGISTRATION NUMBER:CRD42017065447; Pre-results.

Dataset Information

Intellectual Disability and Potassium Channelopathies: A Systematic Review.

Publications

Intellectual Disability and Potassium Channelopathies: A Systematic Review.

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