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Parkin Mutations and Early-Onset Parkinsonism in a Taiwanese Cohort
Ruey-Meei Wu, MD, PhD;
Rebecca Bounds, BSc;
Sarah Lincoln, BSc;
Mary Hulihan, MS;
Chin-Hsien Lin, MD;
Wuh-Liang Hwu, MD, PhD;
Judy Chen, MD;
Katrina Gwinn-Hardy, MD;
Matt Farrer, PhD
Arch Neurol. 2005;62:82-87.
Background Loss of function of the parkin gene (PRKN) is the predominant genetic cause of juvenile and early-onset parkinsonism in Japan, Europe, and the United States.
Objectives To evaluate the frequency of PRKN mutations in Taiwanese (ethnic Chinese) patients with early-onset parkinsonism and to explore genotype-phenotype correlations.
Design Clinical assessment included medical, neurologic, and psychiatric evaluation. Genomic DNA sequencing and quantitative polymerase chain reaction were performed to identify PRKN mutations. Gene expression was examined in patient lymphoblastoid cell lines, in which PRKN mutations were identified.
Patients Forty-one Taiwanese patients with early-onset parkinsonism (aged <50 years at onset).
Results Four of 41 probands had PRKN mutations. One proband had compound heterozygous mutations, with a PRKN exon 2 deletion and an exon 7 G284R substitution. The phenotype resembled typical Parkinson disease. Three patients were mutation carriers. One proband had PRKN exon 2 and exon 3 deletions in the same allele. However, this patient’s phenotype was that of classic "parkin-proven" autosomal recessive juvenile parkinsonism, characterized by symmetrical foot dystonia at onset, gait disturbance, diurnal change, and very slow progression. The 2 remaining carriers had novel heterozygous exon 11 R396G substitutions. Patients with PRKN mutations were younger at onset than those without mutations, and they required a lower dose of levodopa despite longer disease duration.
Conclusions Mutations in PRKN are a rare cause of early-onset parkinsonism in Taiwanese individuals. The overall mutation frequency, adjusted for age at onset, was comparable with that reported for white cohorts; however, the point mutations identified seem to be population specific.
Author Affiliations: Departments of Neurology, Pediatrics, and Medical Genetics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei (Drs Wu, Lin, and Hwu); Department of Medicine, University of California at Los Angeles (Dr Chen); Division of Neurogenetics, National Institute of Neurological Disease and Stroke, Bethesda, Md (Dr Gwinn-Hardy); and Laboratories of Neurogenetics, Department of Neuroscience, Mayo Clinic, Jacksonville, Fla (Dr Farrer and Mss Bounds, Lincoln, and Hulihan).
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