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Severe GBA1 variants drive the GBA1-PD clinical phenotype: implications for counselling and clinical trials
Elisa Menozzi1,2, Sara Lucas Del Pozo1,2, Jane Macnaughtan2,3
1Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London (UCL), London, UK.
Abstract:
Variants in the GBA1 gene are the commonest genetic risk factor for Parkinson disease (PD). Genotype-phenotype correlations exist but with conflicting data. Here, we compared the clinical phenotype of 183 idiopathic PD (iPD) patients, 39 severe GBA1-PD, 24 mild GBA1-PD, and 55 risk GBA1-PD. Compared to iPD, we observed that only severe GBA1-PD patients had a distinctive, more several clinical profile, characterised by worse depression, hyposmia, cognitive dysfunction, and possibly constipation.
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