PD Guide

PARK3

Dopamine

The PARK3 locus (Chr2p13d) is associated with autosomal dominant PD (Gasser et al., 1998). Clinically, affected carriers exhibit features similar to sporadic PD with an age of onset in the 50-60s; some individual also exhibit dementia. Post mortem histopathology of PARK3 cases shows Lewy bodies, tangles and plaques (West et al., 2001). Variation at the PARK3 locus may also influence risk for PD or age of onset (DeStefano et al., 2002).

The identification of the causal gene underlying the PARK3 locus has yet to be identified, but several studies point to a region containing the gene for sepiapterine reductase, the protein product of which is involved in dopamine synthesis (Karamohamed et al., 2003; Sharma et al., 2006).

Reference: 
Gasser T, Müller-Myhsok B, Wszolek ZK, Oehlmann R, Calne DB, Bonifati V, et al. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nat Genet. 1998;18(3):262-5.
West AB, Zimprich A, Lockhart PJ, Farrer M, Singleton A, Holtom B, et al. Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes. Eur J Hum Genet. 2001;9(9):659-66.
DeStefano AL, Lew MF, Golbe LI, Mark MH, Lazzarini AM, Guttman M, et al. PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study. Am J Hum Genet. 2002;70(5):1089-95.
Karamohamed S, DeStefano AL, Wilk JB, Shoemaker CM, Golbe LI, Mark MH, et al. A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the GenePD study. Neurology. 2003;61(11):1557-61.
Sharma M, Mueller JC, Zimprich A, Lichtner P, Hofer A, Leitner P, et al. The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations. J Med Genet. 2006;43(7):557-62.
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