Parkin (PARK 2) mutations are rare in Czech patients with early-onset Parkinson's disease.

Ondrej Fiala,Lenka Pospisilova,Jana Kucerova,Milada Matejckova,Evzen Ruzicka,Pavel Martasek,Daniela Zahorakova,Jan Roth,Oscar Arias-Carrion

doi:10.1371/journal.pone.0107585

Abstract

ObjectiveThe aim of the study is to determine the frequency of parkin allelic variants in Czech early-onset Parkinson's disease patients and healthy controls.MethodsA total of 70 early-onset Parkinson's disease patients (age at onset ≤40 years) and 75 controls were screened for the sequence variants and exon rearrangements in the parkin gene.ResultsParkin mutations were identified in five patients (7.1%): the p.R334C point mutation was present in one patient, four patients had exon deletions. The detected mutations were observed in the heterozygous state except one homozygous deletion of the exon 4. No mutations were obtained in control subjects. A novel sequence variant p.V380I (c.1138G>A) was identified in one control. Non-pathogenic polymorphisms p.S167N and p.D394N were seen in similar percentage in patients and controls, polymorphism p.V380L was almost twice as frequent in controls as in patients.ConclusionsOur study contributes to the growing body of evidence on the low frequency of the parkin mutations in the early-onset Parkinson's disease suggesting the potential role of other genes in the pathogenesis of the disease.

Highlights

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder, clinically characterized by resting tremor, rigidity, and bradykinesia, as well as non-motor impairment such as cognitive deficit or autonomic dysfunction [1]
The mean age at onset (AAO) of PD is usually between 60–70 years [3], 3–5% of all patients with PD have onset before the age 40 years [4]
Described polymorphisms p.S167N and p.D394N were seen in similar percentage in patients (7.1%, 10.0%) and controls (9.3%, 8.0%)

Summary

Introduction

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder, clinically characterized by resting tremor, rigidity, and bradykinesia, as well as non-motor impairment such as cognitive deficit or autonomic dysfunction [1]. The mean age at onset (AAO) of PD is usually between 60–70 years [3], 3–5% of all patients with PD have onset before the age 40 years [4]. This rare form of the disease is referred as early-onset PD (EOPD); the incidence of EOPD is estimated 0.5 per 100 000 per year [5]. The clinical phenotype of EOPD differs from classic PD in several features such as slower disease progression, more frequent occurrence of dystonia, marked sleep benefit, excellent treatment response, and early development of levodopa-induced dyskinesia and motor fluctuations [4,6]. Among several genes whose mutations are associated with autosomal recessive EOPD, parkin mutations were shown as the most common [7]

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Conclusion