Frequency of known mutations in early-onset Parkinson disease: implication for genetic counseling: the consortium on risk for early onset Parkinson disease study.
OBJECTIVE
To assess the frequency and clinical characteristics of carriers of previously identified mutations in 6 genes associated with early-onset Parkinson disease (PD) and provide empirical data that can be used to inform genetic counseling.


METHODS
Cross-sectional observational study.


METHODS
Thirteen movement disorders centers.


METHODS
Nine hundred fifty-three individuals with early-onset PD defined as age at onset (AAO) younger than 51 years. Participants included 77 and 139 individuals of Hispanic and Jewish ancestry, respectively. Intervention Mutations in SNCA, PRKN, PINK1, DJ1, LRRK2, and GBA were assessed. A validated family history interview and the Unified Parkinson Disease Rating Scale were administered. Demographic and phenotypic characteristics were compared among groups defined by mutation status. Main Outcome Measure Mutation carrier frequency stratified by AAO and ethnic background.


RESULTS
One hundred fifty-eight (16.6%) participants had mutations, including 64 (6.7%) PRKN, 35 (3.6%) LRRK2 G2019S, 64 (6.7%) GBA, and 1 (0.2%) DJ1. Mutation carriers were more frequent in those with an AAO of 30 years or younger compared with those with AAO between 31 and 50 years (40.6% vs 14.6%, P < .001), in individuals who reported Jewish ancestry (32.4% vs 13.7%, P < .001), and in those reporting a first-degree family history of PD (23.9% vs 15.1%, P = .01). Hispanic individuals were more likely to be PRKN carriers than non-Hispanic individuals (15.6% vs 5.9%, P = .003). The GBA L444P mutation was associated with a higher mean Unified Parkinson Disease Rating Scale III score after adjustment for covariates.


CONCLUSIONS
Individuals of Jewish or Hispanic ancestry with early-onset PD, those with AAO of 30 years or younger, and those with a history of PD in a first-degree relative may benefit from genetic counseling.
Alcalay
Roy N
RN
Department of Neurology, Columbia University, New York, NY 10032, USA.
Caccappolo
Elise
E
Mejia-Santana
Helen
H
Tang
Ming Xin
MX
Rosado
Llency
L
Ross
Barbara M
BM
Verbitsky
Miguel
M
Kisselev
Sergey
S
Louis
Elan D
ED
Comella
Cynthia
C
Colcher
Amy
A
Jennings
Danna
D
Nance
Martha A
MA
Bressman
Susan B
SB
Scott
William K
WK
Tanner
Caroline
C
Mickel
Susan
S
Andrews
Howard
H
Waters
Cheryl
C
Fahn
Stanley
S
Cote
Lucien
L
Frucht
Steven
S
Ford
Blair
B
Rezak
Michael
M
Novak
Kevin
K
Friedman
Joseph H
JH
Pfeiffer
Ronald
R
Marsh
Laura
L
Hiner
Bradley
B
Siderowf
Andrew
A
Ottman
Ruth
R
Marder
Karen
K
Clark
Lorraine N
LN
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000208:ethnology / Q000235:genetics*; D012044:Regression Analysis; D012306:Risk; D014481:United States / Q000208:ethnology