Worldwide frequency of G2019S LRRK2 mutation in Parkinson's disease: a systematic review.
BACKGROUND
The LRRK2 G2019S mutation is the most frequent known cause of familial and sporadic Parkinson's disease. Knowledge of its worldwide frequency distribution is essential for clinical and molecular research as well as genetic counseling.


OBJECTIVE
To conduct a systematic review of the reported frequency of G2019S in different populations and to assess critically the quality of the clinical studies.


METHODS
We conducted a systematic review of all published papers on G2019S frequency in homogeneous ethnic groups or sub-groups of patients. Selected papers were analyzed for methodological quality.


RESULTS
68 studies from 32 countries were included in the analysis. A heterogeneous distribution was observed with high frequencies in North African Arab countries, the Middle East, southern Europe, North American Ashkenazi Jewish populations and in South American countries with known European ethnic influence. Frequencies ranged from the no cases to 35.7% in sporadic and 42% in familial North-African Arab patients. Only one paper from one sub-Saharan country was found. Methodological pitfalls were identified.


CONCLUSIONS
Estimated frequencies were found to be variable, which may reflect ethnic differences and methodological discrepancies. We make recommendations on the methods of selection of participants and on the definition of familial Parkinson's disease to improve the quality of frequency studies on LRRK2 mutations.
Correia Guedes
L
L
Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon School of Medicine, Lisbon, Portugal. lcorreiaguedes@sapo.pt
Ferreira
J J
JJ
Rosa
M M
MM
Coelho
M
M
Bonifati
V
V
Sampaio
C
C
D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases