Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients

Neuroreport. 2000 Jul 14;11(10):2079-82. doi: 10.1097/00001756-200007140-00004.


Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinson's disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI = 0.36-0.88; p = 0.012, p(c) = 0.047, chi2 = 6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • DNA Mutational Analysis
  • DNA Primers
  • European Continental Ancestry Group
  • Female
  • Genes, Dominant
  • Genetic Carrier Screening
  • Genotype
  • Germany
  • Humans
  • Male
  • Parkinson Disease / enzymology
  • Parkinson Disease / genetics*
  • Polymorphism, Genetic
  • Reference Values
  • Restriction Mapping
  • Thiolester Hydrolases / genetics*
  • Ubiquitin Thiolesterase


  • DNA Primers
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase