Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease.
BACKGROUND
Mutations in the PTEN-induced kinase (PINK1) gene located within the PARK6 locus on chromosome 1p35-p36 have recently been identified in patients with recessive early-onset Parkinson disease.


OBJECTIVE
To assess the prevalence of PINK1 mutations within a series of early- and late-onset Parkinson disease patients living in North America.


METHODS
All coding exons of the PINK1 gene were sequenced in a series of 289 Parkinson disease patients and 80 neurologically normal control subjects; the mutation frequencies were evaluated in additional controls (100 white and 50 Filipino subjects).


RESULTS
We identified 27 variants, including the first reported compound heterozygous mutation (Glu240Lys and Leu489Pro) and a homozygous Leu347Pro mutation in 2 unrelated young-onset Parkinson disease patients.


CONCLUSIONS
Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease.
Rogaeva
Ekaterina
E
Centre for Research in Neurodegenerative Diseases and Division of Neurology, Department of Medicine, Toronto Western Hospital, University of Toronto, Ontario, Canada.
Johnson
Janel
J
Lang
Anthony E
AE
Gulick
Cindy
C
Gwinn-Hardy
Katrina
K
Kawarai
Toshitaka
T
Sato
Christine
C
Morgan
Angharad
A
Werner
John
J
Nussbaum
Robert
R
Petit
Agnes
A
Okun
Michael S
MS
McInerney
Aideen
A
Mandel
Ronald
R
Groen
Justus L
JL
Fernandez
Hubert H
HH
Postuma
Ron
R
Foote
Kelly D
KD
Salehi-Rad
Shabnam
S
Liang
Yan
Y
Reimsnider
Sharon
S
Tandon
Anurag
A
Hardy
John
J
St George-Hyslop
Peter
P
Singleton
Andrew B
AB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D011494:Protein Kinases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase