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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A multi-incident, Old-Order Amish family with PD.

BACKGROUND: PD is largely a sporadic condition of unknown etiology, but specific inherited mutations are a cause of PD. OBJECTIVE: To describe a large, multi-incident Amish pedigree with PD. METHODS: Case ascertainment, calculation of population prevalence, and calculation of kinship coefficients (a measure of relatedness between two individuals) for affecteds and subjects in a large kindred with PD were conducted. Sequencing of genes with known mutations sufficient to cause PD and marker-by-marker haplotype analysis in chromosomal regions flanking previously described genes with known mutations were performed. RESULTS: The authors have examined 113 members of this pedigree and classified 67 as normal (no evidence of PD), 17 as clinically definite PD, 6 as clinically probable PD, and 23 as clinically possible PD. The mean age at onset of the clinically definite subjects was 56.7 years. The phenotype in this family is typical of idiopathic PD, including rest tremor, rigidity, bradykinesia, postural instability, and response to levodopa. In addition, dementia occurred in six of the clinically definite subjects, and many subjects experienced levodopa-related motor complications including wearing off and dopa-induced dyskinesias. In the index Amish community, a minimum prevalence of PD in the population 40 years and older of 552/100,000 was calculated. The mean kinship coefficient in the subjects with PD and those with PD by history (0.036) was higher (p = 0.007) than in a group of age-matched normal Amish control subjects (0.016), providing evidence that PD is inherited in this family. Sequence analysis did not detect any mutations in known PD genes. No single haplotype cosegregates with the disease in any of the chromosomal regions previously found to be linked to PD, and no marker in these regions exhibits increased homozygosity among definite PD cases. CONCLUSIONS: PD in this community is more common than in the general population, and this increased prevalence may be due in part to a novel gene(s).[1]


  1. A multi-incident, Old-Order Amish family with PD. Racette, B.A., Rundle, M., Wang, J.C., Goate, A., Saccone, N.L., Farrer, M., Lincoln, S., Hussey, J., Smemo, S., Lin, J., Suarez, B., Parsian, A., Perlmutter, J.S. Neurology (2002) [Pubmed]
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