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

Janel Johnson, Coro Paisán-Ruíz, Grisel Lopez, Cynthia Crews, Angela Britton, Roniel Malkani, E. Whitney Evans, Aideen McInerney-Leo, Shushant Jain, Robert L. Nussbaum, Kelly D. Foote, Ronald J. Mandel, Anthony Crawley, Sharon Reimsnider, Hubert H. Fernandez, Michael S. Okun, Katrina Gwinn-Hardy, Andrew B. Singleton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)386-391
Number of pages6
JournalNeurodegenerative Diseases
Volume4
Issue number5
DOIs
StatePublished - Jul 2007

Keywords

  • Dardarin encoding
  • LRRK2, Parkinson's disease
  • Mutation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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