title: Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations.
abstract: OBJECTIVE
  Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients.
  
  
  METHODS
  All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients. These variants were evaluated using SIFT, PolyPhen, HSF, and LOVD web-based programs.
  
  
  RESULTS
  The frequency of EOPD-associated variations in the PRKN gene was 34%. Among these variations, p.A82E in exon 3 and p.Q409X in exon 11 was determined to be pathogenic. We also defined previously unknown cryptic variations, including c.872-35 G>A and c.872-28T>G in exon 8 of PRKN and c.252+30 T>G and c.322+4 A>G in exons 4 and 5 of DJ1, respectively, that were associated with EOPD. Although no significant association was observed between the PARK gene mutations and clinical features (P>0.05), the alterations were related to the clinical symptoms in each patient.
  
  
  CONCLUSIONS
  An increasing number of studies report that PRKN, PINK1, DJ1 and SNCA mutations are associated with early-onset Parkinson's disease; however, a limited number of studies have been conducted in Turkey. Additionally, our study is the first to evaluate the frequency of SNCA mutations in a Turkish population. The aim of this study was determine the frequency distributions of the PRKN, PINK1, DJ1, and SNCA gene mutations and to analyze the relationships between these genetic variations and the clinical phenotype of EOPD in Turkish patients.
authors.affiliation: Department of Neurology, Medical Faculty, Uludag University, Bursa, Turkey. Electronic address: sevdaerer@gmail.com.
authors.forename: Sevda
authors.initials: S
authors.lastname: Erer
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Unal
authors.initials: U
authors.lastname: Egeli
authors.affiliation: Department of Neurology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Zarifoglu
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Tezcan
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Cecener
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Tunca
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Secil
authors.initials: S
authors.lastname: Ak
authors.affiliation: Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Demirdogen
authors.affiliation: Erenkoy Traning and Research hospital for neurologic and psychiatric disease, Istanbul, Turkey.
authors.forename: Gulay
authors.initials: G
authors.lastname: Kenangil
authors.affiliation: Department of Neurology, Medical Faculty, Mersin University, Mersin, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kaleagası
authors.affiliation: Department of Neurology, Medical Faculty, Mersin University, Mersin, Turkey.
authors.forename: Okan
authors.initials: O
authors.lastname: Dogu
authors.affiliation: Department of Neurology, Medical Faculty, Hacettepe University, Ankara, Turkey.
authors.forename: Esen
authors.initials: E
authors.lastname: Saka
authors.affiliation: Department of Neurology, Medical Faculty, Hacettepe University, Ankara, Turkey.
authors.forename: Bulent
authors.initials: B
authors.lastname: Elibol
mesh_terms: D000328:Adult; D017668:Age of Onset; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D000071617:Protein Deglycase DJ-1 / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D014421:Turkey; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C105131:PARK7 protein, human
keywords: DJ1; PARK loci; PINK1; PRKN; Parkinsonism; SNCA