Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation

نویسندگان

  • Aikaterina Angeli
  • Niccolo E Mencacci
  • Raquel Duran
  • Iciar Aviles-Olmos
  • Zinovia Kefalopoulou
  • Joseph Candelario
  • Sarah Rusbridge
  • Jennifer Foley
  • Priyanka Pradhan
  • Marjan Jahanshahi
  • Ludvic Zrinzo
  • Marwan Hariz
  • Nicholas W Wood
  • John Hardy
  • Patricia Limousin
  • Tom Foltynie
  • MRCP
  • MD
چکیده

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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عنوان ژورنال:

دوره 28  شماره 

صفحات  -

تاریخ انتشار 2013