Risk of Parkinson disease in carriers of parkin mutations: estimation using the kin-cohort method.
OBJECTIVE
To estimate the risk of Parkinson disease (PD) in individuals with mutations in the Parkin gene.


METHODS
We assessed point mutations and exon deletions and duplications in the Parkin gene in 247 probands with PD (age at onset < or =50 years) and 104 control probands enrolled in the Genetic Epidemiology of Parkinson's Disease (GEPD) study. For each first-degree relative, a consensus diagnosis of PD was established. The probability that each relative carried a mutation was estimated from the proband's Parkin carrier status using Mendelian principles and from the relationship of the relative to the proband.


METHODS
Tertiary care movement disorders center. Patients Cases, controls, and their first-degree relatives were enrolled in the GEPD study.


METHODS
Estimated age-specific penetrance in first-degree relatives.


RESULTS
Parkin mutations were identified in 25 probands with PD (10.1%), 18 (72.0%) of whom were heterozygotes. One Parkin homozygote was reported in 2 siblings with PD. The cumulative incidence of PD to age 65 years in carrier relatives (age-specific penetrance) was estimated to be 7.0% (95% confidence interval, 0.4%-71.9%), compared with 1.7% (95% confidence interval, 0.8%-3.4%) in noncarrier relatives of the cases (P = .59) and 1.1% (95% confidence interval, 0.3%-3.4%) in relatives of the controls (compared with noncarrier relatives, P = .52).


CONCLUSIONS
The cumulative risk of PD to age 65 years in a noncarrier relative of a case with an age at onset of 50 years or younger is not significantly greater than the general population risk among controls. Age-specific penetrance among Parkin carriers, in particular heterozygotes, deserves further study.
Wang
Yuanjia
Y
Department of Biostatistics, Mailman School of Public Health, New York, New York, USA.
Clark
Lorraine N
LN
Louis
Elan D
ED
Mejia-Santana
Helen
H
Harris
Juliette
J
Cote
Lucien J
LJ
Waters
Cheryl
C
Andrews
Howard
H
Ford
Blair
B
Frucht
Steven
S
Fahn
Stanley
S
Ottman
Ruth
R
Rabinowitz
Daniel
D
Marder
Karen
K
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D015994:Incidence; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019683:Penetrance; D011336:Probability; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D018570:Risk Assessment
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases