| Parkinson's disease (PD) is the second most common neurodegenerative disorder. The view that there are genetic contributions to the etiology of PD is supported by research that has found a family history of PD in ten to twenty percent of PD patients, over a dozen genes that cause the rare familial forms of PD and the identification of genetic risk factors from genome-wide association studies. In this study, 22 subjects from a large Mennonite kindred (MEN-1) with multiple cases of parkinsonism and dementia and other neurological disorders were assessed for genetic variants that might contribute to the parkinsonism and dementia phenotype. The in silico analysis of whole-genome sequence from four kindred members showed that previously identified mutations associated with PD and dementia were not present in affected kindred members and was then used to prioritize genetic variants for further analysis. Variants at six candidate genes were identified: ATXN7L1, FRRS1L, MC1R, RANBP2, SNCA and PARK7. Their presence was assessed in the remaining kindred members by direct sequencing of polymerase chain reaction amplification products. The potential contributions of the identified variants to the disease phenotypes seen in the MEN-1 kindred are discussed. |
