To assess the frequency and clinical characteristics of carriers of previously identified mutations in six genes associated with early onset Parkinson disease (EOPD) and provide empirical data that can be used to inform genetic counseling.
Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2 and GBA were assessed in 953 individuals with EOPD ascertained based on age at onset (AAO) ≤50 years. Participants included 77 Hispanics and 139 of Jewish ancestry. A validated family history interview and the Unified Parkinson’s Disease Rating Scale (UPDRS) were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status.
One hundred and fifty eight (16.6%) had mutations including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA and one (0.2%) DJ1. Mutation carriers were more frequent among cases with AAO ≤30 than among cases with AAO between 31 and 50 (40.6% vs. 14.6% p<0.001), Jews compared to non-Jews (32.4% vs. 13.7% p<0.001) and those reporting a first degree family history of PD than among those who did not (23.9% versus 15.1% p=0.012). Hispanics were more likely to be PRKN carriers than non-Hispanics (15.6% versus 5.9% p=0.003). The GBA L444P mutation was associated with a higher mean UPDRS-III score after adjustment for covariates.
EOPD individuals of Jewish or Hispanic ancestry, those with AAO ≤ 30, and those with a family history of PD in a first-degree relative may benefit from genetic counseling.