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Ekaterina Rogaeva, PhD; Janel Johnson, BS; Anthony E. Lang, MD; Cindy Gulick, BS; Katrina Gwinn-Hardy, MD; Toshitaka Kawarai, MD; Christine Sato, MS; Angharad Morgan, PhD; John Werner, BS; Robert Nussbaum, MD; Agnes Petit, PhD; Michael S. Okun, MD; Aideen McInerney, MS; Ronald Mandel, MD; Justus L. Groen; Hubert H. Fernandez, MD; Ron Postuma, MD; Kelly D. Foote, MD; Shabnam Salehi-Rad, MS; Yan Liang, PhD; Sharon Reimsnider, PhD; Anurag Tandon, PhD; John Hardy, PhD; Peter St George-Hyslop, MD; Andrew B. Singleton, PhD

Arch Neurol. 2004;61:1898-1904.

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.

Design  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.

Conclusion  Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease.

Author Affiliations: Centre for Research in Neurodegenerative Diseases (Drs Rogaeva, Kawarai, Morgan, Petit, Liang, Tandon, and St George-Hyslop; Mss Sato and Salehi-Rad; and Mr Groen) and Division of Neurology (Dr Rogaeva), Department of Medicine, and Movement Disorders Centre, Toronto Western Hospital (Drs Lang and Postuma), University of Toronto, and Division of Neurology, Department of Medicine, University Health Network (Drs Lang and St George-Hyslop), Toronto, Ontario; Molecular Genetics Section (Mss Johnson and Gulick and Dr Singleton) and Laboratory of Neurogenetics (Drs Hardy and Singleton), National Institute on Aging, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke (Dr Gwinn-Hardy and Mr Werner), and Genetic Diseases Research Branch, National Human Genome Research Institute (Dr Nussbaum and Ms McInerney), National Institutes of Health, Bethesda, Md; and Movement Disorders Center, Departments of Neurology, Neurosurgery, and Psychiatry, University of Florida, Gainesville (Drs Okun, Mandel, Fernandez, Foote, and Reimsnider).

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