{"doi":"10.1101/2025.06.03.25328628","title":"<i>RAB32</i> -linked Parkinson’s disease: Deep phenotyping, MDSGene literature review, and application of SynNeurGe criteria","abstract":"Abstract Background The RAB32 p.Ser71Arg variant is a novel cause of monogenic Parkinson’s disease (PD), for which detailed phenotypic information is currently scarce. Objectives To clinically and biologically characterize individuals with PARK- RAB32 to gain insights into genotype-phenotype relationships, disease severity, and underlying pathology. Methods We conducted a literature review following the MDSGene database protocol, alongside detailed phenotyping of 11 PARK- RAB32 patients and one prodromal individual from the Rostock International PD (ROPAD) study. In addition to comprehensive scale-based assessments, including olfactory testing, we obtained neuroimaging data and various biomaterials, and performed α-synuclein seeding assays (SAA) in cerebrospinal fluid in a subset. Results 83 patients (74 from the literature) were included in the analysis. The median age at onset was 54 (IQR: 46-61) years. Typical Parkinsonism with a favorable dopaminergic response was observed in all patients. In our cohort, the mean MDS-UPDRS III score was 38.5±21.8 points. Autonomic symptoms were present in all individuals, and 10/11 patients had hyposmia. Several non-motor symptoms were reported for the first time in PARK- RAB32 . Misfolded α-synuclein was identified in 2/2 patients, but not in the prodromal individual. 123I-FP-CIT imaging was available for eight patients, revealing neurodegeneration in all of them. Conclusion While PARK- RAB32 is clinically and likely pathologically similar to idiopathic PD, our study underscores the importance of carefully assessing non-motor symptoms in this newly described form of PD. According to SynNeurGe criteria, PARK- RAB32 is classified as S + (evidence of synucleinopathy), N + (neurodegeneration supported by imaging data), and G F + (presence of a genetic variant).","journal":"medRxiv","year":2025,"id":558148,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7295,"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":1393667,"name":"Francesco Cavallieri","orcid":"0000-0001-5836-1982","position":1,"is_corresponding":false},{"id":249049,"name":"Max Borsche","orcid":"0000-0002-9651-5986","position":2,"is_corresponding":false},{"id":771287,"name":"Giulia Toschi","orcid":"0009-0003-1987-0495","position":3,"is_corresponding":false},{"id":112968,"name":"Franco Valzania","orcid":null,"position":4,"is_corresponding":false},{"id":1393669,"name":"Valentina Fioravanti","orcid":"0000-0003-2741-0512","position":5,"is_corresponding":false},{"id":17510,"name":"Enza Maria Valente","orcid":"0000-0002-0600-6820","position":6,"is_corresponding":false},{"id":1393670,"name":"Pierfrancesco Mitrotti","orcid":"0000-0003-3574-1290","position":7,"is_corresponding":false},{"id":249055,"name":"Micol Avenali","orcid":"0000-0002-7880-9921","position":8,"is_corresponding":false},{"id":1170155,"name":"Simone Zittel","orcid":"0000-0002-3767-6376","position":9,"is_corresponding":false},{"id":1394218,"name":"Rommi Born","orcid":null,"position":10,"is_corresponding":false},{"id":1393671,"name":"Michele Matarazzo","orcid":"0000-0002-2907-8667","position":11,"is_corresponding":false},{"id":112967,"name":"Alessio Di Fonzo","orcid":"0000-0001-6478-026X","position":12,"is_corresponding":false},{"id":1393672,"name":"Edoardo Monfrini","orcid":"0000-0003-4720-9234","position":13,"is_corresponding":false},{"id":1227881,"name":"Mandy Radefeldt","orcid":null,"position":14,"is_corresponding":false},{"id":1393673,"name":"Letizia Santinelli","orcid":"0000-0002-5621-058X","position":15,"is_corresponding":false},{"id":1394219,"name":"Norman Griebner","orcid":null,"position":16,"is_corresponding":false},{"id":1248923,"name":"Cholpon Shambetova","orcid":"0000-0002-2547-315X","position":17,"is_corresponding":false},{"id":1394220,"name":"Max Brand","orcid":null,"position":18,"is_corresponding":false},{"id":72367,"name":"Carolin Gabbert","orcid":"0000-0002-2308-9330","position":19,"is_corresponding":false},{"id":252390,"name":"Cornelis Blauwendraat","orcid":"0000-0001-9358-8111","position":20,"is_corresponding":false},{"id":558553,"name":"Joanne Trinh","orcid":"0000-0001-9863-2070","position":21,"is_corresponding":false},{"id":325979,"name":"Christian Beetz","orcid":"0000-0001-7061-2895","position":22,"is_corresponding":false},{"id":406939,"name":"Peter Bauer","orcid":"0000-0001-9414-4555","position":23,"is_corresponding":false},{"id":249053,"name":"Norbert Brüggemann","orcid":"0000-0001-5969-6899","position":24,"is_corresponding":false},{"id":1192785,"name":"Global Parkinson’s Genetics Program (GP2)","orcid":null,"position":25,"is_corresponding":false},{"id":17492,"name":"Christine Klein","orcid":"0000-0003-2102-3431","position":26,"is_corresponding":false},{"id":1393666,"name":"Teresa Kleinz","orcid":"0009-0000-6313-7395","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:25.969263Z","pmid":"40568674","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":[]}