Clinical prediction of GBA carrier status in Parkinson's disease.

Autor:	Greenberg J; Department of Neurology, New York University Langone Health, New York, NY, USA., Astudillo K; Department of Neurology, New York University Langone Health, New York, NY, USA.; The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, New York University Langone Health, New York, NY, USA., Frucht SJ; Department of Neurology, New York University Langone Health, New York, NY, USA.; The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, New York University Langone Health, New York, NY, USA., Flinker A; Department of Neurology, New York University Langone Health, New York, NY, USA.; Department of Biomedical Engineering, New York University Tandon School of Engineering, New York, NY, USA., Riboldi GM; Department of Neurology, New York University Langone Health, New York, NY, USA.; The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, New York University Langone Health, New York, NY, USA.
Jazyk:	angličtina
Zdroj:	Clinical parkinsonism & related disorders [Clin Park Relat Disord] 2024 Apr 11; Vol. 10, pp. 100251. Date of Electronic Publication: 2024 Apr 11 (Print Publication: 2024).
DOI:	10.1016/j.prdoa.2024.100251
Abstrakt:	Introduction: Given the unique natural history of GBA -related Parkinson's disease ( GBA -PD) and the potential for novel treatments in this population, genetic testing prioritization for the identification of GBA -PD patients is crucial for prognostication, individualizing treatment, and stratification for clinical trials. Assessing the predictive value of certain clinical traits for the GBA -variant carrier status will help target genetic testing in clinical settings where cost and access limit its availability. Methods: In-depth clinical characterization through standardized rating scales for motor and non-motor symptoms and self-reported binomial information of a cohort of subjects with PD (n = 100) from our center and from the larger cohort of the Parkinson's Progression Marker Initiative (PPMI) was utilized to evaluate the predictive values of clinical traits for GBA variant carrier status. The model was cross-validated across the two cohorts. Results: Leveraging non-motor symptoms of PD, we established successful discrimination of GBA variants in the PPMI cohort and study cohort (AUC 0.897 and 0.738, respectively). The PPMI cohort model successfully generalized to the study cohort data using both MDS-UPDRS scores and binomial data (AUC 0.740 and 0.734, respectively) while the study cohort model did not. Conclusions: We assessed the predictive value of non-motor symptoms of PD for identifying GBA carrier status in the general PD population. These data can be used to determine a simple, clinically oriented model using either the MDS-UPDRS or subjective symptom reporting from patients. Our results can inform patient counseling about the expected carrier risk and test prioritization for the expected identification of GBA variants. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giulietta Maria Riboldi reports financial support was provided by Prevail Therapeutics. G.R. is supported by grants from Michael J Fox Foundation, Parkinson’s Foundation, Department of Defense (PD210038), NIH (R01NS116006, R01NS133742), and received a previous research grant from Prevail Therapeutics. A.F. is supported by grants from the NIH (R01NS109367, R01DC018805, R01NS115929) and NSF (CRCNS 1912286). J.G., K.A., and S.F. report no specific funding related to this work. Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report. (© 2024 The Authors. Published by Elsevier Ltd.)
Databáze:	MEDLINE
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