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PRKN , DJ‐1 , and PINK1 screening identifies novel splice site mutation in PRKN and two novel DJ‐1 mutations
Author(s) -
Ghazavi Farzaneh,
Fazlali Zeinab,
Banihosseini Setareh Sadat,
Hosseini SayedRzgar,
Kazemi Mohammad Hossein,
Shojaee Seyedmehdi,
Parsa Khosro,
Sadeghi Homa,
Sina Farzad,
Rohani Mohammad,
Shahidi GholamAli,
Ghaemi Nasser,
Ronaghi Mostafa,
Elahi Elahe
Publication year - 2011
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23417
Subject(s) - genetics , exon , mutation , rna splicing , biology , allele , gene , mutation testing , microbiology and biotechnology , compound heterozygosity , polymerase chain reaction , rna
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. © 2010 Movement Disorder Society.