LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans.
BACKGROUND
Mutations in leucine-rich repeat kinase 2 gene (LRRK2), particularly the G2019S mutation in exon 41, have been detected in familial and sporadic Parkinson disease (PD) cases.


OBJECTIVE
To assess the frequency of LRRK2 exon 41 mutations in a series of sporadic PD cases from Europe and to determine the clinical features of LRRK2 mutation carriers.


METHODS
We analyzed European cases of sporadic PD for the presence of LRRK2 exon 41 mutations. These mutations were screened by denaturing high-performance liquid chromatography, and abnormal chromatograph traces were investigated by direct sequencing to determine the exact nature of the variants. Early-onset sporadic PD cases were also screened for parkin mutations. The haplotypes associated with the G2019S mutation were determined. The clinical characteristics of patients carrying LRRK2 mutations were detailed.


METHODS
French Network for the Study of Parkinson Disease Genetics. Patients Three hundred twenty patients with apparently sporadic PD from Europe.


METHODS
Results of genetic analyses.


RESULTS
We found the G2019S mutation in 6 patients and identified 2 new variants (Y2006H and T2031S) in 1 patient each. Their clinical features were similar to those of typical PD. All G2019S mutation carriers shared a common haplotype.


CONCLUSIONS
The G2019S mutation is almost as frequent in sporadic cases (1.9%) as in previously reported familial cases (2.9%) in Europe and occurs in the same common founder. We identified 2 novel variants. Although the phenotype of LRRK2 mutation carriers closely resembles that of typical PD, the age at onset was younger (29 years in 1 patient) than previously described, and 3 patients were improved by deep brain stimulation.
Lesage
Suzanne
S
Institut National de la Santé et de la Recherche Médicale Unité 679, Neurology and Experimental Therapeutics, and Faculté de Médecine, Université Pierre et Marie Curie, 75651 Paris CEDEX 13, France.
Janin
Sabine
S
Lohmann
Ebba
E
Leutenegger
Anne-Louise
AL
Leclere
Laurence
L
Viallet
François
F
Pollak
Pierre
P
Durif
Franck
F
Thobois
Stéphane
S
Layet
Valérie
V
Vidailhet
Marie
M
Agid
Yves
Y
Dürr
Alexandra
A
Brice
Alexis
A
Bonnet
Anne-Marie
AM
Borg
Michel
M
Broussolle
Emmanuel
E
Damier
Philippe
P
Destée
Alain
A
Martinez
Maria
M
Penet
Christiane
C
Rasco
Olivier
O
Tison
François
F
Tranchan
Christine
C
Vérin
Marc
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods; D005060:Europe; D005091:Exons / Q000235:genetics*; D005260:Female; D006639:Histidine / Q000235:genetics; 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*; D012694:Serine / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014443:Tyrosine / Q000235:genetics
D013912:Threonine; D014443:Tyrosine; D012694:Serine; D006639:Histidine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases