The leucine rich repeat kinase 2 (LRRK2) G2019S substitution mutation. Association with Parkinson disease, malignant melanoma and prevalence in ethnic groups in Israel.
BACKGROUND
A single missense mutation (G2019S) in the leucine rich repeat kinase 2 (LRRK2) gene has been reported to be prevalent among Ashkenazi Jewish patients with Parkinson disease (PD). An association between malignant melanoma (MM) and PD was also recently reported. The nature of this association is still elusive.


OBJECTIVE
To evaluate the rate of the G2019S(*) LRKK2 mutation among ethnically diverse, Jewish PD patients, MM patients, and Ashkenazi, Iraqi and Moroccan healthy controls.


METHODS
Overall, 242 Jewish PD patients (155 Ashkenazim and 7 of mixed origin) and 169 Jewish MM patients (142 Ashkenazim) were genotyped for the G2019S mutation. In addition, 900 healthy ethnic Jewish controls (300 Ashkenazim, 300 Moroccans and 300 Iraqis) were similarly analyzed. Genotyping was performed using PCR amplification followed by restriction digest and gel electrophoresis. Statistical analysis was done using the Chi square test.


RESULTS
Overall 19/242 (7.9 %) of the PD patients (16/155 of Ashkenazim, 10.3 %; 3/87 of non-Ashkenazim, 3.4 %) harbored the G2019S LRKK2 mutation. The age at diagnosis of PD in mutation carriers was 60.6 +/- 10.9 years compared with an age at diagnosis of 61.1 +/- 13.4 years in non-carriers (p = 0.87). Nine of 38 familial Ashkenazi PD patients (23.68 %) carried the mutation, as did 2/169 MM patients (1.2 %; 2/142, 1.4 % of the Ashkenazim). A single mutation carrier of Ashkenazi origin was detected among 900 controls (0.3 % of the Ashkenazi controls).


CONCLUSIONS
The G2019S*LRKK2 mutation is significantly more prevalent in Ashkenazi PD patients than in controls (p = 1 x 10(-6)), it is less commonly detected in non-Ashkenazi affected individuals, and its contribution to MM predisposition in Jewish individuals needs to be explored further.
The Parkinson's Disease and Movement Disorders Clinic, Dept. of Neurology and Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. shassin@post.tau.ac.il
Sharon
S
Hassin-Baer
Yael
Y
Laitman
Esther
E
Azizi
Irena
I
Molchadski
Gilli
G
Galore-Haskel
Frida
F
Barak
Oren S
OS
Cohen
Eitan
E
Friedman
D000367:Age Factors; D000368:Aged; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics*; 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