Mutation analysis of the PINK1 gene in 391 patients with Parkinson disease.
OBJECTIVE
To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations.


METHODS
Retrospective clinical and genetic review.


METHODS
University hospital.


METHODS
We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries.


RESULTS
We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p.D297MfsX22 and p.W437R] and 5 single heterozygous mutations [p.A78V, p.P196QfsX25, p.M342V, p.W437R, and p.N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations.


CONCLUSIONS
Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.
Kumazawa
Ryuya
R
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Tomiyama
Hiroyuki
H
Li
Yuanzhe
Y
Imamichi
Yoko
Y
Funayama
Manabu
M
Yoshino
Hiroyo
H
Yokochi
Fusako
F
Fukusako
Toshihiro
T
Takehisa
Yasushi
Y
Kashihara
Kenichi
K
Kondo
Tomoyoshi
T
Elibol
Bulent
B
Bostantjopoulou
Sevasti
S
Toda
Tatsushi
T
Takahashi
Hirohide
H
Yoshii
Fumihito
F
Mizuno
Yoshikuni
Y
Hattori
Nobutaka
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase