parkin mutation analysis in clinic patients with early-onset Parkinson's disease

P. Poorkaj, J. G. Nutt, D. James, S. Gancher, T. D. Bird, E. Steinbart, G. D. Schellenberg, Haydeh Payami

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49 Scopus citations


parkin mutations are the most common identified cause of Parkinson's disease (PD). It has been suggested that patients with young-onset PD be screened for parkin mutations as a part of their clinical work-up. The aim of this study was to assess parkin mutation frequency in a clinical setting, correlate genotype with phenotype, and evaluate the current justification for clinical parkin testing. Patients were selected from a movement disorder clinic based on diagnosis of PD and onset age ≤ 40 years. parkin was genotyped by sequence and dosage analysis for all 12 exons. Key relatives and controls were screened for identified mutations. Mutations were found in 7/39 patients. Two patients were compound heterozygous; five were heterozygous. Mutations included deletions in exons 2, 3, and 8, duplications in exons 2-4, and 9, and P437L substitution. Seventy-eight percent of mutations were deletions/multiplications. A novel substitution (R402W) was found in one patient and in one control. None of the point mutations found in patients were detected in 96 controls. parkin phenotypes were consistent with idiopathic PD. In conclusion, parkin mutations are common in the clinic setting. 10% of PD patients had early-onset and 18% of them had parkin mutations. However, if parkin is recessive, only 5% of early-onset cases who had compound mutations could be attributed to this locus. Mutation frequency was 0.12 (95% CI 0.04-0.19). parkin cases can present as typical idiopathic PD, distinguishable only by molecular testing. Seventy percent of parkin cases were heterozygous. It is unclear whether heterozygous mutations are pathogenic. parkin-based diagnosis and counseling require a better understanding of the mode of inheritance, penetrance, and carrier frequencies.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalAmerican Journal of Medical Genetics
Volume129 A
Issue number1
StatePublished - Aug 15 2004


  • Clinical testing
  • Gene dosage
  • Parkinson's disease
  • parkin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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