{"doi":"10.14802/jmd.25247","title":"Clinical and Pathological Features of CSF1R-Related Disorder Associated With the p.R777Q Pathogenic Variant","abstract":"OBJECTIVE: Colony-stimulating factor-1 receptor (CSF1R)-related disorder (CSF1R-RD) is a rapidly progressive neurodegenerative disease with a median onset of 43 years. More than 200 CSF1R pathogenic variants have been identified. Patients develop rapidly progressive dementia and motor symptoms, with a median disease duration of 6.8 years. The p.R777Q variant causes CSF1R-RD; it is deleterious to protein function. We describe the clinical and pathological features of CSF1R-RD associated with p.R777Q and report a new family carrying this variant. We compare the neuropathological findings of an index patient (with short-duration disease) with those of a patient with long-duration CSF1R-RD. METHODS: We present clinical and imaging data from a new family with p.R777Q. We also describe the neuropathology of an index patient and contrast these findings with features of a patient with CSF1R-RD with an 11-year disease course caused by the c.2656_2657insC variant. RESULTS: We reviewed the literature on 13 individuals from 8 families with the p.R777Q variant from Asia, Europe, and North America. The mean age at onset was 41±14 years, ranging from 22 to 63 years, and the mean survival was 3.3±2.5 years. Neuropathologic studies of our index patient (10-month disease duration) revealed features consistent with CSF1R-RD. Axonal and myelin pathology was severe in the periventricular white matter. Compared with the patient with an 11-year disease duration, the index patient had less severe white matter lesions. CONCLUSION: Compared with CSF1R-RD associated with other variants, the p.R777Q variant has an aggressive course. Compared with the patient with a long disease duration, the index patient had milder neuropathological findings. These differences may be specific to p.R777Q or associated with rapid clinical progression.","journal":"Journal of Movement Disorders","year":2025,"id":581242,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":961839,"name":"Delaney Liskey","orcid":null,"position":1,"is_corresponding":false},{"id":505040,"name":"Audrey Strongosky","orcid":"0000-0003-4734-0339","position":2,"is_corresponding":false},{"id":428948,"name":"Stuart J. McCarter","orcid":"0000-0001-8158-8835","position":3,"is_corresponding":false},{"id":1492550,"name":"Paula Sandroni","orcid":"0009-0000-4208-1230","position":4,"is_corresponding":false},{"id":54753,"name":"Dennis W. Dickson","orcid":"0000-0001-7189-7917","position":5,"is_corresponding":false},{"id":17548,"name":"Zbigniew K. Wszołek","orcid":"0000-0001-5487-1053","position":6,"is_corresponding":false},{"id":1434731,"name":"Tomasz Chmiela","orcid":"0000-0001-6022-7731","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T02:58:47.357782Z","pmid":"41233991","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}