title: Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers.
abstract: OBJECTIVE
  Glucocerebrosidase (GBA) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in GBA mutation carriers, which represents a key issue for genetic counseling, especially for relatives of patients with Gaucher disease (GD), is unknown. Our objective was to estimate PD penetrance in a familial study of GBA mutation carriers.
  
  
  METHODS
  Probands with familial PD were recruited through the French Parkinson Disease Genetic Study Group. All GBA exons were sequenced in probands and their relatives. To estimate the age-specific cumulative PD risk (i.e., penetrance) in GBA mutation carriers, we used the proband's phenotype exclusion likelihood method and corrected for selection of familial cases by considering the status of one affected relative per family as unknown.
  
  
  RESULTS
  Of 525 probands with familial PD, 24 (4.6%) were GBA mutation carriers. Of their 256 relatives, 43 (16.8%) had PD and 26 of 32 affected relatives tested for GBA mutations were mutation carriers; 213 relatives did not have PD and 31 of 71 of unaffected relatives tested for GBA mutations were mutation carriers. Under a dominant model, penetrance was estimated as 7.6%, 13.7%, 21.4%, and 29.7% at 50, 60, 70, and 80 years, respectively. There was no significant difference in penetrance at 70 years between N370S carriers, L444P carriers, and carriers of rarer mutations.
  
  
  CONCLUSIONS
  The relatively high penetrance estimate in GBA carriers obtained in this study should lead to consideration of GBA as a dominant causal gene with reduced penetrance and should be taken into account for genetic counseling in relatives of patients with GD and patients with GBA-associated PD.
authors.affiliation: INSERM, U975, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Anheim
authors.forename: A
authors.initials: A
authors.lastname: Elbaz
authors.forename: S
authors.initials: S
authors.lastname: Lesage
authors.forename: A
authors.initials: A
authors.lastname: Durr
authors.forename: C
authors.initials: C
authors.lastname: Condroyer
authors.forename: F
authors.initials: F
authors.lastname: Viallet
authors.forename: P
authors.initials: P
authors.lastname: Pollak
authors.forename: B
authors.initials: B
authors.lastname: Bonaïti
authors.forename: C
authors.initials: C
authors.lastname: Bonaïti-Pellié
authors.forename: A
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D019683:Penetrance; D010641:Phenotype
chemical_list: D005962:Glucosylceramidase