Background: Homozygous glucocerebrosidase mutations cause Gaucher disease, whereas heterozygous mutations are the most important genetic risk factor for Parkinson's disease (PD). The penetrance of heterozygous glucocerebrosidase mutations for PD is variable (10%–30%), depends on the population studied, and has only been assessed in Gaucher disease or familial PD. The aim of this study was to assess the penetrance of glucocerebrosidase mutations in PD in unselected PD patients. Methods: The penetrance of glucocerebrosidase mutations was estimated using the kin-cohort method. Results: Data on family history were available for 63 of 123 PD glucocerebrosidase mutation carriers, identified among 2843 unrelated consecutive PD patients. Three hundred eighty-one first-degree relatives were analyzed. The risk of developing PD was 10% at 60 years, 16% at 70 years, and 19% at 80 years. Conclusions: The estimated penetrance of glucocerebrosidase mutations in unselected PD patients is higher than that estimated in Gaucher disease cohorts and lower than that estimated in familial PD cohorts. © 2020 International Parkinson and Movement Disorder Society.

Penetrance of Glucocerebrosidase (GBA) Mutations in Parkinson's Disease: A Kin Cohort Study

Balestrino R.;Lopiano L.;
2020

Abstract

Background: Homozygous glucocerebrosidase mutations cause Gaucher disease, whereas heterozygous mutations are the most important genetic risk factor for Parkinson's disease (PD). The penetrance of heterozygous glucocerebrosidase mutations for PD is variable (10%–30%), depends on the population studied, and has only been assessed in Gaucher disease or familial PD. The aim of this study was to assess the penetrance of glucocerebrosidase mutations in PD in unselected PD patients. Methods: The penetrance of glucocerebrosidase mutations was estimated using the kin-cohort method. Results: Data on family history were available for 63 of 123 PD glucocerebrosidase mutation carriers, identified among 2843 unrelated consecutive PD patients. Three hundred eighty-one first-degree relatives were analyzed. The risk of developing PD was 10% at 60 years, 16% at 70 years, and 19% at 80 years. Conclusions: The estimated penetrance of glucocerebrosidase mutations in unselected PD patients is higher than that estimated in Gaucher disease cohorts and lower than that estimated in familial PD cohorts. © 2020 International Parkinson and Movement Disorder Society.
35
11
2111
2114
GBA; genetics; glucocerebrosidase; Parkinson's disease; penetrance
Balestrino R.; Tunesi S.; Tesei S.; Lopiano L.; Zecchinelli A.L.; Goldwurm S.
File in questo prodotto:
File Dimensione Formato  
BALESTRINO.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 267.47 kB
Formato Adobe PDF
267.47 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1763200
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 24
social impact