Genetic analysis of LRRK2 functional domains in Brazilian patients with Parkinson's disease.
OBJECTIVE
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been associated with Parkinson's disease (PD), and the majority of the pathogenic variants are located in the ROC and MAPKKK domains.


METHODS
Exons 29-31 and 38-44 (ROC and MAPKKK domains) were sequenced in 204 patients with PD, mostly Brazilian.


RESULTS
We identified four polymorphisms, a novel silent variant p.R1398R and four substitutions: p.T1410M, p.G2019S, p.Y2189C and the novel variant p.C2139S.


CONCLUSIONS
The most prevalent mutation was the p.G2019S (2.4%). We consider that the p.T1410M and the p.Y2189C variants are probably polymorphisms and that the p.C2139S mutation is potentially pathogenic.
Abdalla-Carvalho
C B
CB
Serviço de Genética Humana, Departamento de Genética, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Santos-Rebouças
C B
CB
Guimarães
B C
BC
Campos
M
M
Pereira
J S
JS
de Rosso
A L Zuma
AL
Nicaretta
D H
DH
Marinho e Silva
M
M
dos Santos
Mendonça J
MJ
Pimentel
M M G
MM
D000368:Aged; D001938:Brazil; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases