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Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation
Author(s) -
Angeli Aikaterina,
Mencacci Niccolo E.,
Duran Raquel,
AvilesOlmos Iciar,
Kefalopoulou Zinovia,
Candelario Joseph,
Rusbridge Sarah,
Foley Jennifer,
Pradhan Priyanka,
Jahanshahi Marjan,
Zrinzo Ludvic,
Hariz Marwan,
Wood Nicholas W.,
Hardy John,
Limousin Patricia,
Foltynie Tom
Publication year - 2013
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25535
Subject(s) - deep brain stimulation , parkin , parkinson's disease , phenotype , disease , glucocerebrosidase , levodopa , genotype , population , medicine , age of onset , genetic heterogeneity , bioinformatics , genetics , biology , gene , environmental health
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.