LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance.
BACKGROUND
Several pathogenic mutations in the LRRK2 gene have been implicated in familial and sporadic cases of Parkinson disease (PD). The R1441G mutation is frequent in Spanish patients of Basque ethnicity with PD, and the G2019S mutation is a common mutation found in several populations worldwide.


OBJECTIVE
To determine the frequency of the LRRK2 G2019S and R1441G mutations in PD patients from the non-Basque northeast region of Spain (Catalonia), and to characterize their family history and clinical features.


METHODS
We screened patients for the presence of the LRRK2 R1441G and G2019S mutations. These LRRK2 mutations were detected by restriction endonuclease digestion, and samples with an abnormal electrophoresis pattern were sequenced to identify the exact nucleotide change. The clinical features and family history of patients with LRRK2 mutations were studied in detail.


METHODS
The northeast region of Spain. Patients Three hundred two patients with PD.


METHODS
Onset age, clinical features, and family history of PD and LRRK2 mutations.


RESULTS
The R1441G mutation was present in 0.7% of total PD cases. The G2019S mutation was found in 6.4% of familial and 3.4% of sporadic cases. Additionally, we found 1 patient with the R1441C mutation. Age at onset ranged from 33 to 78 years. Clinical features were not different from classic PD, except for 1 patient who presented with monosymptomatic leg rest tremor of 8 years' duration. In addition, a 91-year-old unaffected relative of a patient with the G2019S mutation was found to be a mutation carrier.


CONCLUSIONS
The G2019S mutation frequency in PD patients from northeast Spain is similar to that reported in other European regions. The R1441G mutation is very uncommon in Catalonia. The presence of an aged unaffected G2019S mutation carrier supports the previously described occurrence of incomplete penetrance in PD patients with LRRK2 mutations.
Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain.
Carles
C
Gaig
Mario
M
Ezquerra
Maria Jose
MJ
Marti
Esteban
E
Muñoz
Francesc
F
Valldeoriola
Eduardo
E
Tolosa
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics; D013030:Spain / Q000453:epidemiology
D012694:Serine; D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine