{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Di Rocco M"],"funding":["Italian National Institute of Health","National Research Council","NIH HHS"],"pagination":["929-941"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8947233"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31(6)"],"pubmed_abstract":["Dominant GNAO1 mutations cause an emerging group of childhood-onset neurological disorders characterized by developmental delay, intellectual disability, movement disorders, drug-resistant seizures and neurological deterioration. GNAO1 encodes the α-subunit of an inhibitory GTP/GDP-binding protein regulating ion channel activity and neurotransmitter release. The pathogenic mechanisms underlying GNAO1-related disorders remain largely elusive and there are no effective therapies. Here, we assessed the functional impact of two disease-causing variants associated with distinct clinical features, c.139A > G (p.S47G) and c.662C > A (p.A221D), using Caenorhabditis elegans as a model organism. The c.139A > G change was introduced into the orthologous position of the C. elegans gene via CRISPR/Cas9"],"journal":["Human molecular genetics"],"pubmed_title":["Caenorhabditis elegans provides an efficient drug screening platform for GNAO1-related disorders and highlights the potential role of caffeine in controlling dyskinesia."],"pmcid":["PMC8947233"],"funding_grant_id":["NUTR-AGE-FOE2019-DSB.AD004.271","2020-2022_ISS20-0ab01a06bd2a","P40 OD010440"],"pubmed_authors":["Caprini D","Lanza E","Bocchinfuso G","Folli V","Leuzzi V","Martinelli S","Di Rocco M","Friedman J","Galosi S","Tosato F","Martire A","Di Schiavi E"],"additional_accession":[]},"is_claimable":false,"name":"Caenorhabditis elegans provides an efficient drug screening platform for GNAO1-related disorders and highlights the potential role of caffeine in controlling dyskinesia.","description":"Dominant GNAO1 mutations cause an emerging group of childhood-onset neurological disorders characterized by developmental delay, intellectual disability, movement disorders, drug-resistant seizures and neurological deterioration. GNAO1 encodes the α-subunit of an inhibitory GTP/GDP-binding protein regulating ion channel activity and neurotransmitter release. The pathogenic mechanisms underlying GNAO1-related disorders remain largely elusive and there are no effective therapies. Here, we assessed the functional impact of two disease-causing variants associated with distinct clinical features, c.139A > G (p.S47G) and c.662C > A (p.A221D), using Caenorhabditis elegans as a model organism. The c.139A > G change was introduced into the orthologous position of the C. elegans gene via CRISPR/Cas9","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-30T20:56:45.313Z","creation":"2025-04-04T10:01:51.94Z"},"accession":"S-EPMC8947233","cross_references":{"pubmed":["34622282"],"doi":["10.1093/hmg/ddab296"]}}