RAB32 bağlantılı Parkinson hastalığı: Derin fenotipleme, MDSGene literatürü incelemesi ve SynNeurGe kriterlerinin uygulanması

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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).

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