Pathogenicity of the Lrrk2 R1514Q substitution in Parkinson's disease.
An increasing number of nonsynonymous LRRK2 variants are being reported as putative pathogenic mutations. We identified one large kindred harboring the Lrrk2 R1514Q substitution; however, the variant did not segregate fully with disease. Combined analyses of three case-control series demonstrate that the R1514Q substitution is not associated with increased risk of disease (OR: 1.3; 95% CI: 0.6-2.8; P = 0.45). These findings highlight the importance of using family-based studies and multiple population screenings when examining the association of these polymorphic LRRK2 gene variants with Parkinson's disease.
Toft
Mathias
M
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Mata
Ignacio F
IF
Ross
Owen A
OA
Kachergus
Jennifer
J
Hulihan
Mary M
MM
Haugarvoll
Kristoffer
K
Stone
Jeremy T
JT
Blazquez
Marta
M
Gibson
J Mark
JM
Aasly
Jan O
JO
White
Linda R
LR
Lynch
Timothy
T
Adler
Charles H
CH
Gwinn-Hardy
Katrina
K
Farrer
Matthew J
MJ
D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D005973:Glutamine; D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases