Whole Exome Sequencing in Familial Parkinson Disease

We have an ongoing study that has recruited families having at least a sibling pair with Parkinson disease (PD). Families have been screened for mutations in known PD causative genes (LRRK2, parkin, etc). Following review of families without a causative mutation, we selected families for whole exome sequencing that had the strongest history of PD and with the most definitive diagnosis. All families have at least 3 affected family members who were evaluated as part of this study. Only affected family members were included for whole exome sequencing.]]> Family members were evaluated, whenever possible, in person using a series of standard case report forms. The UK Brain Bank criteria were implemented as a Diagnostic Checklist (Pankratz et al., 2002) and all individuals included for sequencing met the modified UK Brain Bank criteria. The modified criteria allows for a family history of PD.]]> This study ascertained families having 2 living siblings diagnosed with Parkinson disease (PD). The families were screened for mutations in known genes (Nichols et al., Lancet, 2005; Pankratz et al., Neurology, 2009). Linkage analysis (Pankratz et al., HMG, 2003) was performed as well as a genomewide association study (Pankratz et al., Human Genetics, 2009).]]>