Comprehensive Screening of a North American Parkinson's Disease Cohort for LRRK2 Mutation

Background Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective To identify mutations causing Parkinson’s disease (PD) in a cohort of North Americans with familial PD. Methods We sequenced exons 1–51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2