title: Second mutation in PARK2 is absent in patients with sporadic Parkinson's disease and heterozygous exonic deletions/duplications in parkin gene.
abstract: OBJECTIVE
  Mutations in PARK2 are one of the causes of Parkinson's disease (PD). Deletions and duplications/triplications of one exon or exon groups account for a large proportion of mutations in the gene. At the present time, it is still not fully clear whether heterozygous mutations cause the development of PD. Our study aimed at conducting screening for mutations in PARK2 in patients with a sporadic form of PD to clarify the role of PARK2 in the development of PD.
  
  
  METHODS
  The cohort of 327 patients with PD was screened by quantitative real-time polimerase chain reaction (PCR) with subsequent Sanger sequencing.
  
  
  RESULTS
  It was found that a sufficiently large proportion of these patients (21 patients, 6.4%) were carriers of heterozygous deletions or duplications in PARK2. Analysis of PARK2 exon rearrangement carriers for the presence of point mutations in PARK2 did not reveal any variants with pathogenic significance.
  
  
  CONCLUSIONS
  Thus, our data indicate that heterozygous deletions and duplications can play an important role in the pathogenesis of PD and can be considered as dominant mutations with low penetrance.
authors: a Department of Molecular Basics of Human Genetics , Institute of Molecular Genetics, Russian Academy of Sciences , Moscow , Russia.
authors: Marina V
authors: http://orcid.org/0000-0003-1274-2901
authors: MV
authors: Shulskaya
authors: a Department of Molecular Basics of Human Genetics , Institute of Molecular Genetics, Russian Academy of Sciences , Moscow , Russia.
authors: Maria I
authors: http://orcid.org/0000-0002-4544-6183
authors: MI
authors: Shadrina
authors: b Department of Neurogenetics , Federal State Scientific Institution 'Scientific Center of Neurology' , Moscow , Russia.
authors: Ekaterina Yu
authors: EY
authors: Fedotova
authors: b Department of Neurogenetics , Federal State Scientific Institution 'Scientific Center of Neurology' , Moscow , Russia.
authors: Nataliya Yu
authors: NY
authors: Abramycheva
authors: a Department of Molecular Basics of Human Genetics , Institute of Molecular Genetics, Russian Academy of Sciences , Moscow , Russia.
authors: Svetlana A
authors: http://orcid.org/0000-0002-1697-6820
authors: SA
authors: Limborska
authors: b Department of Neurogenetics , Federal State Scientific Institution 'Scientific Center of Neurology' , Moscow , Russia.
authors: Sergey N
authors: SN
authors: Illarioshkin
authors: a Department of Molecular Basics of Human Genetics , Institute of Molecular Genetics, Russian Academy of Sciences , Moscow , Russia.
authors: Petr A
authors: http://orcid.org/0000-0003-3530-0655
authors: PA
authors: Slominsky
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: PARK2; Parkinson's disease; exon rearrangements; point mutations