Roberta Balestrino1, Sara Tunesi2, Silvana Tesei3, Leonardo Lopiano1, Anna L Zecchinelli3, Stefano Goldwurm3. 1. Department of Neuroscience "Rita Levi Montalcini", University of Turin, Torino, Italy. 2. Unit of Medical Statistics and Epidemiology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy, and CPO-Piedmont, Novara, Italy. 3. Parkinson Institute, ASST "Pini-CTO", Milano, Italy.
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.
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.
Authors: Eileen E Moran; Susan B Bressman; Roberto A Ortega; Deborah Raymond; William C Nichols; Christina A Palmese; Sonya Elango; Matthew Swan; Vicki Shanker; Imali Perera; Cuiling Wang; Molly E Zimmerman; Rachel Saunders-Pullman Journal: Front Neurol Date: 2021-02-26 Impact factor: 4.003
Authors: Roberto A Ortega; Cuiling Wang; Deborah Raymond; Nicole Bryant; Clemens R Scherzer; Avner Thaler; Roy N Alcalay; Andrew B West; Anat Mirelman; Yuliya Kuras; Karen S Marder; Nir Giladi; Laurie J Ozelius; Susan B Bressman; Rachel Saunders-Pullman Journal: JAMA Netw Open Date: 2021-04-01
Authors: Fabian J David; Miranda J Munoz; Jay L Shils; Michael W Pauciulo; Philip T Hale; William C Nichols; Mitra Afshari; Sepehr Sani; Leo Verhagen Metman; Daniel M Corcos; Gian D Pal Journal: Front Neurol Date: 2021-09-30 Impact factor: 4.003