title: A "dose" effect of mutations in the GBA gene on Parkinson's disease phenotype.
abstract: Mutations in the GBA gene are associated with Parkinson's disease (PD). A definite description of the clinical characteristics of PD patients who are compound heterozygotes or homozygotes for mutations in the GBA gene (GD-PD) requires further elucidation.
  
  
  
  We assessed motor, cognitive, olfactory and autonomic functions as well as demographic data and medical history in a cohort of Ashkenazi Jewish PD patients who were screened for seven common mutations in the GBA gene. We then compared three groups of patients (matched for age and disease duration) who were distinguished by their GBA mutation status, idiopathic PD (iPD), GBA heterozygote PD (GBA-PD) and GD-PD.
  
  
  
  Out of a total of 1050 AJ PD patients screened, 12 were found to be either homozygotes or compound heterozygotes for mutations in the GBA gene. These patients had an earlier age of onset, more severe motor impairment, poorer cognition and lower olfactory scores. They also had a higher prevalence of REM sleep behavior disorder and higher frequencies of hallucinations compared to both GBA-PD and iPD.
  
  
  
  The severity of PD phenotype is related to the burden of GBA mutations with GD-PD patients manifesting a more severe phenotype.
authors.affiliation: Movement Disorders Unit, Neurological Institute, Tel-Aviv Sourasky Medical Center, Israel; Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address: avnerth@gmail.com.
authors.forename: Avner
authors.initials: A
authors.lastname: Thaler
authors.affiliation: Movement Disorders Unit, Neurological Institute, Tel-Aviv Sourasky Medical Center, Israel; Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tanya
authors.initials: T
authors.lastname: Gurevich
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bar Shira
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: Mali
authors.initials: M
authors.lastname: Gana Weisz
authors.affiliation: Memory and Attention Disorders Center, Neurological Institute, Tel Aviv Sourasky Medical Center Israel.
authors.forename: Elissa
authors.initials: E
authors.lastname: Ash
authors.affiliation: Memory and Attention Disorders Center, Neurological Institute, Tel Aviv Sourasky Medical Center Israel.
authors.forename: Tamara
authors.initials: T
authors.lastname: Shiner
authors.affiliation: Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel; Genetic Institute, Tel Aviv Sourasky Medical Center, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.affiliation: Movement Disorders Unit, Neurological Institute, Tel-Aviv Sourasky Medical Center, Israel; Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Giladi
authors.affiliation: Movement Disorders Unit, Neurological Institute, Tel-Aviv Sourasky Medical Center, Israel; Sackler School of Medicine, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Mirelman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis / Q000235:genetics; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype
chemical_list: D005962:Glucosylceramidase
keywords: GBA; Gaucher's disease; Parkinson's disease