title: Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics.
abstract: The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (+/- 2SE) in patients was 0.013 +/- 0.006 overall, 0.030 +/- 0.019 in familial PD, 0.007 +/- 0.005 in nonfamilial PD, 0.016 +/- 0.013 in early-onset PD, and 0.012 +/- 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date.
authors.affiliation: Genomics Institute, Wadsworth Center, New York State Department of Health, Albany, 12201, USA.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Kay
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Factor
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Ali
authors.initials: A
authors.lastname: Samii
authors.forename: Alida
authors.initials: A
authors.lastname: Griffith
authors.forename: Tom D
authors.initials: TD
authors.lastname: Bird
authors.forename: Patricia
authors.initials: P
authors.lastname: Kramer
authors.forename: Donald S
authors.initials: DS
authors.lastname: Higgins
authors.forename: Haydeh
authors.initials: H
authors.lastname: Payami
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000453:epidemiology / Q000235:genetics; D009154:Mutation; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine