title: 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.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Janel
authors.initials: J
authors.lastname: Johnson
authors.forename: Coro
authors.initials: C
authors.lastname: Paisán-Ruíz
authors.forename: Grisel
authors.initials: G
authors.lastname: Lopez
authors.forename: Cynthia
authors.initials: C
authors.lastname: Crews
authors.forename: Angela
authors.initials: A
authors.lastname: Britton
authors.forename: Roniel
authors.initials: R
authors.lastname: Malkani
authors.forename: E Whitney
authors.initials: EW
authors.lastname: Evans
authors.forename: Aideen
authors.initials: A
authors.lastname: McInerney-Leo
authors.forename: Shushant
authors.initials: S
authors.lastname: Jain
authors.forename: Robert L
authors.initials: RL
authors.lastname: Nussbaum
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Foote
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Mandel
authors.forename: Anthony
authors.initials: A
authors.lastname: Crawley
authors.forename: Sharon
authors.initials: S
authors.lastname: Reimsnider
authors.forename: Hubert H
authors.initials: HH
authors.lastname: Fernandez
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.forename: Katrina
authors.initials: K
authors.lastname: Gwinn-Hardy
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D001923:Brain Chemistry / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009656:North America; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D005819:Genetic Markers; D022821:RNA Splice Sites; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases