Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation |
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Authors: | Aikaterina Angeli MD Niccolo E. Mencacci MD Raquel Duran MD Iciar Aviles‐Olmos MD Zinovia Kefalopoulou MD PhD Joseph Candelario BSc Sarah Rusbridge BSc Jennifer Foley PhD Priyanka Pradhan PhD Marjan Jahanshahi PhD Ludvic Zrinzo MD PhD Marwan Hariz MD PhD Nicholas W. Wood PhD FRCP John Hardy PhD FRS FMedSci Patricia Limousin MD PhD Tom Foltynie MRCP MD |
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Affiliation: | 1. Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, , London, United Kingdom;2. Reta Lila Weston Laboratories and Departments of Molecular Neuroscience, UCL Institute of Neurology, , London, United Kingdom;3. Department of Neurology and Laboratory of Neuroscience, “Dino Ferrari” Centre, Università degli Studi di Milano‐IRCCS Istituto Auxologico Italiano, , Milan, Italy;4. Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, , London, United Kingdom |
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Abstract: | Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l ‐dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype‐phenotype relationships. |
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Keywords: | genetics Parkinson's disease phenotype deep brain stimulation heterogeneity |
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