Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation.

ABSTRACT

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.