{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bhagat SL"],"funding":["NIBIB NIH HHS","NIA NIH HHS","Bachmann-Strauss Dystonia and Parkinson Foundation","NINDS NIH HHS","National Institutes of Health","Jake's Ride","NIH","NIH HHS","NIGMS NIH HHS","Medical Scientist Training Program"],"pagination":["137-45"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4939622"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["93"],"pubmed_abstract":["Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the significance of a rare missense variant in the Tor1a gene (c. 613T>A, p. F205I), previously identified in a patient with sporadic late-onset focal dystonia, by modeling it in mice. Homozygous F205I mice have motor impairment, reduced steady-state levels of TorsinA, altered corticostriatal synaptic plasticity, and prominent brain imaging abnormalities in areas associated with motor function. Thus, the F205I variant causes abnormalities in domains affected in people and/or mouse "],"journal":["Neurobiology of disease"],"pubmed_title":["Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models."],"pmcid":["PMC4939622"],"funding_grant_id":["R21 NS072707","T32-746-GM007171","K01AG041211-03","K01 AG041211","NS072707-01A1","P41 EB 015897","P41 EB015897","1S10OD010683-01","S10 OD010683","T32 GM007171"],"pubmed_authors":["Bhagat SL","Calakos N","Wetsel WC","Pan Y","Rodriguiz RM","Badea A","Qiu S","Caffall ZF","Wan Y","Hochgeschwender U"],"additional_accession":[]},"is_claimable":false,"name":"Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models.","description":"Rare de novo mutations in genes associated with inherited Mendelian disorders are potential contributors to sporadic disease. DYT1 dystonia is an autosomal dominant, early-onset, generalized dystonia associated with an in-frame, trinucleotide deletion (n. delGAG, p. ΔE 302/303) in the Tor1a gene. Here we examine the significance of a rare missense variant in the Tor1a gene (c. 613T>A, p. F205I), previously identified in a patient with sporadic late-onset focal dystonia, by modeling it in mice. Homozygous F205I mice have motor impairment, reduced steady-state levels of TorsinA, altered corticostriatal synaptic plasticity, and prominent brain imaging abnormalities in areas associated with motor function. Thus, the F205I variant causes abnormalities in domains affected in people and/or mouse ","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Sep","modification":"2025-04-26T14:05:52.312Z","creation":"2019-03-27T02:18:08Z"},"accession":"S-EPMC4939622","cross_references":{"pubmed":["27168150"],"doi":["10.1016/j.nbd.2016.05.003"]}}