title: PRKN, DJ-1, and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ-1 mutations.
abstract: We present results of mutation screening of PRKN gene in 93 Iranian Parkinson's disease (PD) patients with average age at onset (AAO) of 42.2 years. The gene was screened by direct sequencing and by a semi-quantitative PCR protocol for detection of sequence rearrangements. Heterozygous rearrangements were tested by reverse transcription-polymerase chain reaction (RT-PCR). Nine different PRKN mutations were found. One of these, IVS9+1G>A, affects splicing and is novel. Two mutated PRKN alleles were observed in each of 6 patients whose average AAO was 25.7 years. Only 1 patient carried a single mutated allele and his AAO was 41 years. Among patients with AAO of <30 years, 31.3% had two mutated alleles, while only 2.6% with AAO of >30 years carried a PRKN mutation. Analysis of PRKN by RT-PCR led to identification of a novel exon expressed in leukocytes of control and PD individuals. The alternatively spliced transcript if translated would code a protein without a RING Finger 2 domain. Its functional relevance remains to be shown. DJ-I and PINK1 were also screened. Two novel DJ-1 mutations, c.91-2A>G affecting splicing and c.319G>C causing Ala107Pro, were observed among patients with AAO of <31 years, suggesting that PD in a high fraction (>12%) of this group of Iranian patients may be due to mutations in DJ-1. Mutations in PINK1 were not observed. Our results complement previous findings on LRRK2 mutations among Iranian PD patients.
authors.affiliation: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Ghazavi
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Fazlali
authors.forename: Setareh Sadat
authors.initials: SS
authors.lastname: Banihosseini
authors.forename: Sayed-Rzgar
authors.initials: SR
authors.lastname: Hosseini
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Kazemi
authors.forename: Seyedmehdi
authors.initials: S
authors.lastname: Shojaee
authors.forename: Khosro
authors.initials: K
authors.lastname: Parsa
authors.forename: Homa
authors.initials: H
authors.lastname: Sadeghi
authors.forename: Farzad
authors.initials: F
authors.lastname: Sina
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rohani
authors.forename: Gholam-Ali
authors.initials: GA
authors.lastname: Shahidi
authors.forename: Nasser
authors.initials: N
authors.lastname: Ghaemi
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ronaghi
authors.forename: Elahe
authors.initials: E
authors.lastname: Elahi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007492:Iran; D007783:Lactones; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D013729:Terpenes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007783:Lactones; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D013729:Terpenes; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C548573:genepolide; C111567:parkin protein; C105131:PARK7 protein, human