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).
Racette
B A
BA
Department of Neurology and Neurological, Washington University School of Medicine, St. Louis, MO 63110, USA. racetteb@neuro.wustl.edu
Rundle
M
M
Wang
J C
JC
Goate
A
A
Saccone
N L
NL
Farrer
M
M
Lincoln
S
S
Hussey
J
J
Smemo
S
S
Lin
J
J
Suarez
B
B
Parsian
A
A
Perlmutter
J S
JS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D012067:Religion