title: Parkin mutations and early-onset parkinsonism in a Taiwanese cohort.
abstract: 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.
  
  
  OBJECTIVE
  To evaluate the frequency of PRKN mutations in Taiwanese (ethnic Chinese) patients with early-onset parkinsonism and to explore genotype-phenotype correlations.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan. rmwu@ha.mc.ntu.edu.tw
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bounds
authors.forename: Sarah
authors.initials: S
authors.lastname: Lincoln
authors.forename: Mary
authors.initials: M
authors.lastname: Hulihan
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Lin
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Judy
authors.initials: J
authors.lastname: Chen
authors.forename: Katrina
authors.initials: K
authors.lastname: Gwinn-Hardy
authors.forename: Matt
authors.initials: M
authors.lastname: Farrer
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005192:Family Health; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009460:Neurologic Examination; D020734:Parkinsonian Disorders / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013624:Taiwan; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D001120:Arginine; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D005998:Glycine