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To the Editor:
Nichols et al. report novel sequence variants in the LRRK2 gene detected in patients with Parkinson disease (PD), and they highlight that additional data are required to determine whether these variants represent pathogenic mutations or rare neutral variants.1 An accurate evaluation of pathogenicity of novel variants identified in patients is crucial not only to build hypotheses about disease mechanisms but also to assist in counseling of patients.
In the Introduction, Nichols et al. state that “Although rare in most populations, the R1441G and G2385R mutations are found at higher rates in the Basque region of Spain and the Han Chinese, respectively.” We originally reported that the G2385R variant is a polymorphism, present in heterozygous state in ∼5% of the Han Chinese population in Taiwan, but it is significantly more common in sporadic PD from that population.2
We proposed the G2385R variant as a risk factor for PD. This association was since replicated in different large samples from the Chinese and Japanese populations (cumulative OR ∼2).3 Thus, G2385R might represent an important genetic risk …
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