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mutation disease parkinson patient study lrrk 2 mutations family variant lrrk 2 g 2019s mutation control population lrrk 2 gene parkinsonism protein chapter disorder analysis tremor g 2019s carrier neurology onset haplotype disord frequency fonzo brain parkinson disease arg 1628pro variant subject pd cases genet cause neurol movement parkin di fonzo region lrrk 2 mutation kinase risk factor chinese syndrome proband domain factor 1628pro 2385arg pd patients result department gly 2385arg variant association effect linkage feature penetrance pathology genetic autosomal italian identi prevalence orthostatic tremor gly 2019ser mutation lrrk 2 protein phenotype university sample evidence hospital basque 1441h ziekte van parkinson legs syndrome 2019ser italy mutatie activity