Chapter 7 - Parkinsonism

Summary

Parkinson's disease (PD) appears as a sporadic disorder in most patients. This chapter discusses the genetics of the Mendelian forms of PD identified to date, focusing on five genes: a-synuclein, parkin, DJ-1, PINK1, and LRRK2 that have been associated conclusively with this disease. Other chromosomal loci including PARK3, PARK10, and PARK11 have been identified by genome-wide approaches, and these regions might harbor further genes for PD. For a few other genes including UCH-L1, NR4A2, SNCAIP, HtrA2/Omi, and GBA there is weaker evidence of association with PD. These loci and genes are also briefly discussed. Emerging data delineate mutations in the LRRK2 gene as the cause of up to 10% of the familial late onset autosomal dominant PD forms, and also of a few sporadic cases. The importance of genetic testing for PD patients is expected to increase in the near future, also raising important ethical issues.