Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jan;2(1):a008888.
doi: 10.1101/cshperspect.a008888.

Genetics of Parkinson's disease

Christine Klein  1 , Ana Westenberger
Affiliations
Review

Genetics of Parkinson's disease

Christine Klein et al. Cold Spring Harb Perspect Med. 2012 Jan.

Abstract

Fifteen years of genetic research in Parkinson's disease (PD) have led to the identification of several monogenic forms of the disorder and of numerous genetic risk factors increasing the risk to develop PD. Monogenic forms, caused by a single mutation in a dominantly or recessively inherited gene, are well-established, albeit relatively rare types of PD. They collectively account for about 30% of the familial and 3%-5% of the sporadic cases. In this article, we will summarize the current knowledge and understanding of the molecular genetics of PD. In brief, we will review familial forms of PD, basic genetic principles of inheritance (and their exceptions in PD), followed by current methods for the identification of PD genes and risk factors, and implications for genetic testing.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Pedigrees showing different inheritance patterns. (A) Autosomal dominant disease inheritance pattern. Every affected person in the pedigree has one affected parent, one affected individual is present in every generation, and on average, an affected individual transmits the mutant gene (and thus the disease) to half of his or her children. (B) Autosomal recessive disease inheritance pattern. The affected individuals have two unaffected parents (both heterozygous mutation carriers), children of the affected individual are also unaffected and heterozygous, and only one of the four siblings (25%) is affected. (C) Autosomal dominant pedigree complicated by the presence of reduced penetrance (not all individuals with a mutation are affected), variable expressivity (not all individuals with a mutation show the expected disorder phenotype), and phenocopies (some individuals show clinical symptoms of the disorder without carrying the disease-causing mutation). Black symbols - affected individuals; white symbols - unaffected individuals; half-filled symbols - individuals with only resting tremor and/or bradykinesia.
Figure 2.
Figure 2.
Pedigree of a PD family that comprises affected members with and without the LRRK2 p.G2019S mutation. Five mutation carriers are unaffected, showing reduced penetrance, two mutation carriers are affected with dystonia, showing variable expressivity, and one affected family member does not have the p.G2019S mutation in LRRK2. Black symbols - affected individuals; white symbols - unaffected individuals; half-filled symbols - individuals with dystonia; + - mutation carriers.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahn TB, Kim SY, Kim JY, Park SS, Lee DS, Min HJ, Kim YK, Kim SE, Kim JM, Kim HJ, et al. 2008. α-Synuclein gene duplication is present in sporadic Parkinson disease. Neurology 70: 43–49 - PubMed
    1. Anderson PC, Daggett V 2008. Molecular basis for the structural instability of human DJ-1 induced by the L166P mutation associated with Parkinson’s disease. Biochemistry 47: 9380–9393 - PMC - PubMed
    1. Athanassiadou A, Voutsinas G, Psiouri L, Leroy E, Polymeropoulos MH, Ilias A, Maniatis GM, Papapetropoulos T 1999. Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding α-synuclein. Am J Hum Genet 65: 555–558 - PMC - PubMed
    1. Bertoncini CW, Fernandez CO, Griesinger C, Jovin TM, Zweckstetter M 2005. Familial mutants of α-synuclein with increased neurotoxicity have a destabilized conformation. J Biol Chem 280: 30649–30652 - PubMed
    1. Bonifati V, Rohe CF, Breedveld GJ, Fabrizio E, De Mari M, Tassorelli C, Tavella A, Marconi R, Nicholl DJ, Chien HF, et al. 2005. Early-onset parkinsonism associated with PINK1 mutations: Frequency, genotypes, and phenotypes. Neurology 65: 87–95 - PubMed

Publication types

LinkOut - more resources