A study of LRRK2 mutations and Parkinson's disease in Brazil.
Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are known as a common cause of Parkinson's disease (PD) among patients from different geographic origins. In this study, we evaluated the prevalence of LRRK2 mutations in exons 31 and 41 in a cohort of 154 consecutive, unrelated Brazilian patients with familial or sporadic PD, including early and late onset patients. The LRRK2 p.G2019S mutation was present in heterozygous state in three index cases (approximately 2%), and in three additional relatives. No carriers of this mutation were found among 250 control chromosomes. Clinically, all mutation-positive patients presented a typical PD phenotype and a good response to levodopa. Mutation segregation analysis in a large sibling showed incomplete penetrance of the p.G2019S. Our findings suggest that the LRRK2 p.G2019S mutation has a substantial contribution to PD susceptibility among Brazilian population and add new clues to current research of this disease.
Pimentel
Márcia Mattos Gonçalves
MM
Serviço de Genética Humana, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, RJ, Brazil. pimentel@uerj.br
Moura
Karla Cristina Vasconcelos
KC
Abdalla
Cláudia Bueno
CB
Pereira
João Santos
JS
de Rosso
Ana Lúcia Zuma
AL
Nicaretta
Denise Hack
DH
Campos
Mário
M
de Almeida
Richard Morais
RM
dos Santos
Jussara Mendonça
JM
Bastos
Izabel Cristina Constantino
IC
Mendes
Maria Filomena Xavier
MF
Maultasch
Henryk
H
Costa
Flavio Henrique de Rezende
FH
Werneck
Antônio Luiz dos Santos
AL
Santos-Rebouças
Cíntia Barros
CB
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001938:Brazil / Q000453:epidemiology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D015995:Prevalence; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
D000978:Antiparkinson Agents; D005819:Genetic Markers; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases