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Mutations in leucine-rich repeat kinase 2 (LRRK2) (PARK8) are associ-ated with both familial and sporadic forms of Parkinson’s disease. Most studies have shown that LRRK2 mutations may explain between 5% and 13% of familial and 1–5% of sporadic Parkinson’s disease. Importantly, a common recurrent mutation (G2019S) located in the kinase domain has been reported across most ethnic populations, with the highest prevalence among Ashkenazi Jews and North African Arabs. | ỊFEBS Journal MINIREVIEW LRRK2 in Parkinson s disease genetic and clinical studies from patients Udhaya Kumari1 2 and E. K. Tan1 2 1 Department of Neurology Singapore General Hospital Singapore Singapore 2 NationalNeuroscience Institute Duke-NUS Graduate Medical School Singapore Singapore Keywords LRRK2 mutations Parkinson s disease penetrance polymorphisms Correspondence E.-K. Tan Department of Neurology Singapore General Hospital Outram Road Singapore 169608 Singapore Fax 65 6220 3321 Tel 65 6326 5003 E-mail gnrtek@sgh.com.sg Received 30 May 2009 revised 27 July 2009 accepted 6 August 2009 doi 10.1111 j.1742-4658.2009.07344.x Mutations in leucine-rich repeat kinase 2 LRRK2 PARK8 are associated with both familial and sporadic forms of Parkinson s disease. Most studies have shown that LRRK2 mutations may explain between 5 and 13 of familial and 1-5 of sporadic Parkinson s disease. Importantly a common recurrent mutation G2019S located in the kinase domain has been reported across most ethnic populations with the highest prevalence among Ashkenazi Jews and North African Arabs. A recent worldwide meta-analysis pooling data from 24 populations reported a higher occurrence of G2019S in southern than in northern European countries and the penetrance is estimated to be 75 at the age of 79 years. The R1441 hotspot amino acid codon residue G H C in the Ras of complex proteins domain is the second most common site of pathogenic LRRK2 substitutions after G2019S with most carriers developing symptoms by the age of 75 years. Two polymorphic variants found almost exclusively among Asians G2385R and R1628P have been shown to increase the Parkinson s disease risk by approximately two-fold. The mutational event associated with R1628P is more recent occurring 2500 years ago compared to estimates of 4000 years for G2385R carriers. LRRK2 mutation carriers generally simulate late onset Parkinson s disease and present with the usual typical clinical features. Genetic testing for G2019S
