A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease.
Mutations in the LRRK2 gene have been identified in families with autosomal dominant parkinsonism. We amplified and sequenced the coding region of LRRK2 from genomic DNA by PCR, and identified a heterozygous mutation (Gly2019 ser) present in four of 61 (6.6%) unrelated families with Parkinson's disease and autosomal dominant inheritance. The families originated from Italy, Portugal, and Brazil, indicating the presence of the mutation in different populations. The associated phenotype was broad, including early and late disease onset. These findings confirm the association of LRRK2 with neurodegeneration, and identify a common mutation associated with dominantly inherited Parkinson's disease.
Di Fonzo
Alessio
A
Department of Clinical Genetics, Erasmus MC Rotterdam, PO Box 1738, 3000 DR Rotterdam, Netherlands.
Rohé
Christan F
CF
Ferreira
Joaquim
J
Chien
Hsin F
HF
Vacca
Laura
L
Stocchi
Fabrizio
F
Guedes
Leonor
L
Fabrizio
Edito
E
Manfredi
Mario
M
Vanacore
Nicola
N
Goldwurm
Stefano
S
Breedveld
Guido
G
Sampaio
Cristina
C
Meco
Giuseppe
G
Barbosa
Egberto
E
Oostra
Ben A
BA
Bonifati
Vincenzo
V
D000328:Adult; D017668:Age of Onset; D000368:Aged; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases