Family studies suggest a 2-fold relative risk for Parkinson's disease (PD) in a first degree relative of a sufferer (1).
Monogenic forms, caused by a single mutation in a dominantly or recessively inherited gene, are well-established, albeit relatively rare types of PD
- collectively account for about 30% of the familial and 3%-5% of the sporadic cases
Pathologically, PD is characterized by loss of dopaminergic neurons in the Substantia nigra pars compacta, deposition of alph-synuclein visualized in the forms of Lewy bodies and Lewy neurites, and neuroinflammation demonstrated by the activation of microglia
- therefore, identifying factors that contribute to the formation and spreading of alpha-synuclein aggregates may be critical to the overall understanding of pathogenesis of PD
- alpha-Synuclein (SNCA) and LRRK2 genes harbor autosomal dominant mutations that cause familial PD with clinical characteristics similar to sporadic PD
Reference:
- Marder K, Tang MX, Mejia H, et al. Risk of Parkinson's disease among first-degree relatives: A community-based study. Neurology 1996;47(1):155-60.
- Lesage S, Dürr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A. French Parkinson's Disease Genetics Study Group. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med. 2006;354:422-423.
- Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D, Paisan-Ruiz C, Lichtner P, Scholz SW, Hernandez DG, Krüger R, Federoff M, Klein C, Goate A, Perlmutter J, Bonin M, Nalls MA, Illig T, Gieger C, Houlden H, Steffens M, Okun MS, Racette BA, Cookson MR, Foote KD, Fernandez HH, Traynor BJ, Schreiber S, Arepalli S, Zonozi R, Gwinn K, van der Brug M, Lopez G, Chanock SJ, Schatzkin A, Park Y, Hollenbeck A, Gao J, Huang X, Wood NW, Lorenz D, Deuschl G, Chen H, Riess O, Hardy JA, Singleton AB, Gasser T. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat Genet. 2009;41:1308-1312.